Viscoelastic composition for securing the visual field of an endoscope

Abstract

To provide a method for securing a visual field of an endoscope, when the visual field of the endoscope is blocked since dark liquid with no visibility or a semisolid material is accumulated inside a pipe, or when the visual field of the endoscope is blocked due to continuous bleeding inside the pipe.SOLUTION: There is provided a viscoelastic composition for securing a visual field of an endoscope containing a viscoelastic material and water, which is a viscoelastic composition having a shear storage modulus G' of 0.7 Pa or higher. The visual field of the endoscope is secured by sending the viscoelastic composition from the hand of the endoscope to the tip of the endoscope through a channel.SELECTED DRAWING: Figure 4B

Description

[Technical field]

[0001] The present invention relates to a viscoelastic composition suitable for use in securing an endoscopic field of view and a method for securing an endoscopic field of view using the viscoelastic composition, and more particularly to a viscoelastic composition suitable for use in securing an endoscopic field of view by pushing aside dark-colored liquid or semisolid matter that is obstructed by accumulation of the liquid or semisolid matter inside a tube, or for securing an endoscopic field of view when the endoscopic field of view is obstructed by continuous bleeding inside a tube, and a method for securing an endoscopic field of view using the viscoelastic composition. [Background technology]

[0002] Endoscopes are used to observe the inside of thin tubes such as the digestive tract and the bile duct. However, when dark liquids that block light, such as blood, intestinal fluid, or bile, or semi-solid matter such as food residue or excrement, accumulate inside the tube, the field of view of the endoscope is blocked, and the state inside the tube cannot be observed sufficiently. In such cases, the field of view of the endoscope has been conventionally secured by supplying water or air to the inside of the tube. Water supply is a method of injecting water, such as distilled water or tap water, into the tube to wash away the liquid or semi-solid matter inside the tube. With this method, the field of view is temporarily secured by removing the liquid or semi-solid matter inside the tube, but the removed liquid or semi-solid matter mixes with the water, and the suspended opaque liquid is diffused inside the tube, so that the field of view is still often insufficient. Air supply is a method of supplying gas, such as air or carbon dioxide, into the tube to remove the liquid or semi-solid matter inside the tube. However, even with this method, although a field of vision is temporarily secured by removing the liquid and semi-solid material inside the tube, if a bleeding area is present, it is difficult to remove the blood and the field of vision is not secured, resulting in problems such as difficulty in identifying the bleeding area and performing hemostasis procedures.

[0003] To address this problem, it has been reported that a transparent jelly drink that can be easily injected through the forceps port of an endoscope but has a viscosity that does not immediately mix with blood or residue is injected through the forceps port, and after filling the lumen of the treatment site with the jelly, the jelly is slowly and continuously injected without using air supply, using a BioShield irrigator (US Endoscopy) as a forceps plug, even while inserting the treatment tool, thereby ensuring the visual field in emergency endoscopy (Non-Patent Documents 1 and 2). It has also been reported that the visual field of an endoscope is ensured by using a viscoelastic composition containing a thickening substance and water, particularly a viscoelastic composition with a loss tangent (tan δ) of 0.6 or less (Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2017 / 057504 [Non-patent literature]

[0005] [Non-Patent Document 1] Tomonori Yano et al., "Gel immersion endoscopy: a new method for securing the visual field during emergency endoscopy," Progress of Digestive Endoscopy, June 1, 2015, Vol. 87, Supplement, p. s85 [Non-Patent Document 2] YANO T, et al., "Gel immersion endoscopy: a novel method to secure the visual field during endoscopy in bleeding patients (with videos)," Gastrointestinal Endoscopy, April 2016, Vol. 83, No. 4, pp. 809-811 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a viscoelastic composition suitable for use in securing an endoscopic field of view, and a method for securing an endoscopic field of view using the viscoelastic composition. More specifically, an object of the present invention is to provide a viscoelastic composition suitable for use in securing an endoscopic field of view by pushing aside dark-colored liquid or semisolid matter that is difficult to see through and accumulates inside a tube, thereby obstructing the endoscopic field of view, or for use in securing an endoscopic field of view when the endoscopic field of view is obstructed by persistent bleeding inside a tube, and a method for securing an endoscopic field of view using the viscoelastic composition. More specifically, the inventors have found that when a composition having a high viscosity is used to ensure an endoscopic visual field, although it may be possible to temporarily push aside liquids or semi-solid matter, the liquids or semi-solid matter that have been physically pushed aside may return to the visual field in a short period of time due to diffusion or suspension, resulting in difficulty in ensuring the desired visual field; and when a composition having a high viscosity is used, if there is persistent bleeding in or around the visual field of the endoscope and the blood is released into the composition filling the lumen, the blood may diffuse and suspend within the composition in a short period of time, resulting in difficulty in ensuring the desired visual field. Therefore, an object of the present invention is to provide a viscoelastic composition that does not have such drawbacks, and a method for ensuring an endoscopic visual field using the viscoelastic composition. [Means for solving the problem]

[0007] As a result of intensive research aimed at solving the above-mentioned problems, the inventors have surprisingly found that when a composition having a shear storage modulus G' of 0.7 Pa or more is used, regardless of the loss tangent (tan δ), a viscoelastic composition suitable for use in ensuring an endoscopic visual field and a method for ensuring an endoscopic visual field using the viscoelastic composition can be obtained, and have completed the present invention described below.

[0008] [1] A viscoelastic composition for ensuring a visual field in an endoscope, comprising a viscosity-increasing substance and water, the viscoelastic composition having a shear storage modulus G' of 0.7 Pa or more. [2] The viscoelastic composition according to [1], having a shear storage modulus G' of 7.0 Pa or less. [3] The viscoelastic composition according to [1] or [2], wherein the thickening substance is a polysaccharide or a hydrophilic polymer. [4] The viscoelastic composition according to any one of [1] to [3], wherein the viscoelastic composition has a loss tangent of greater than 0.6. [5] The viscoelastic composition according to any one of [1] to [4], which is colorless and transparent. [6] The viscoelastic composition according to any one of [1] to [5], feeding the endoscope from the proximal end of the endoscope through a channel to the distal end of the endoscope; How to ensure endoscopic visibility. [7] The method according to [6], wherein the endoscope is a medical endoscope. Effect of the Invention

[0009] The viscoelastic composition of the present invention can be suitably used for securing the visual field of an endoscope. Specifically, when the viscoelastic composition of the present invention is injected into the inside of a tube through a channel of an endoscope, the elastic component of the viscoelastic composition can physically push aside liquids such as blood, intestinal fluid, and bile, and semi-solids such as food residue and excrement. In addition, the viscoelastic composition of the present invention has a property of being difficult to mix with the liquids and semi-solids due to the elastic component, so that the liquids and semi-solids that have been physically pushed aside can be prevented from returning to the visual field in a short time due to diffusion or suspension. Furthermore, because of the property of being difficult to mix with the above-mentioned liquids and semi-solids, when there is persistent bleeding in or around the visual field of the endoscope and the blood is released into the composition filling the lumen, the viscoelastic composition of the present invention can prevent the blood from diffusing and suspending in the composition in a short time, and as a result, it is possible to maintain a clear visual field for a relatively long time. [Brief description of the drawings]

[0010] [Figure 1] FIG. 2 is a photograph of a proximal portion of a medical endoscope. [Figure 2A]FIG. 1 is a conceptual diagram showing the state inside a bleeding digestive tract. [Figure 2B] FIG. 1 is a conceptual diagram showing the state when water is pumped into a bleeding digestive tract. [Diagram 3] FIG. 13 is a diagram showing an example of a camera image obtained when water is injected into the digestive tract through the forceps port of the endoscope. [Figure 4A] FIG. 1 is a conceptual diagram showing the state inside a bleeding digestive tract. [Figure 4B] 1 is a conceptual diagram showing the state when the viscoelastic composition of the present invention is delivered into a bleeding digestive tract. [Diagram 5] FIG. 2 is a diagram showing an example of a camera image obtained when the viscoelastic composition of the present invention is injected into the digestive tract through the forceps port of an endoscope. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The viscoelastic composition of the present invention contains a thickening material and water.

[0012] The "thickening substance" of the present invention means a substance that has the effect of increasing viscosity when dissolved or dispersed in water. The thickening substance of the present invention may be composed of one type of component or a combination of two or more types of components. Examples of such thickening substances include alcohols such as methanol, ethanol, 2-propanol, 1,4-butanediol, 1,3-butylene glycol, propylene glycol, glycerin catechin, glucose, fructose, galactose, sucrose, lactose, maltose, trehalose, xylitol, sorbitol, mannitol, glucosamine, and galactosamine;Aureobasidium culture solution, amacead gum, gum arabic, arabinogalactan, alginic acid and its salts, propylene glycol alginate, welan gum, cassia gum, ghatti gum, curdlan, carrageenan, karaya gum, xanthan gum, guar gum, guar gum enzyme hydrolysate, psyllium seed gum, desert mugwort seed gum, gellan gum, succinoglycan, tamarind gum, tara gum, tragacanth gum, furcellaran, funoran, pullulan, pectin, macrophomopsis gum, rhamsan gum, locust bean gum, acrylic Acid starch, acetylated adipate crosslinked starch, acetylated oxidized starch, acetylated phosphate crosslinked starch, sodium octenylsuccinate starch, carboxymethylcellulose and its salts, carboxymethylethylcellulose, starch acetate, oxidized starch, sodium starch glycolate, hydroxypropylated phosphate crosslinked starch, hydroxypropylcellulose, hydroxypropyl starch, hydroxypropylmethylcellulose, hydroxymethylcellulose, hydroxyethylmethylcellulose, hydroxyethylcellulose, Ethyl cellulose, methyl cellulose, cellulose, phosphate crosslinked starch, phosphorylated starch, phosphate monoesterified phosphate crosslinked starch, fucoidan, diutan gum, glucomannan, hyaluronic acid and its salts, keratan sulfate, heparin, chondroitin sulfate, dermatan sulfate, scleroglucan, schizophyllan, okra extract, aloe arborescens extract, sesbania gum, agarose, agaropectin, amylose, amylopectin, pregelatinized starch, inulin, levan, graminan, agar, hydrophobized hydroxypropyl methylcellulose polysaccharides such as cellulose, dextran, dextrin, croscarmellose sodium, glucuronoxylan, arabinoxylan; proteins such as gelatin, hydrolyzed gelatin, collagen; polyamino acids such as polyglutamic acid, polylysine, polyaspartic acid; hydrophilic polymers such as carboxyvinyl polymers, polyacrylic acid and its salts, partially neutralized polyacrylic acid, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, polyethylene glycol, polypropylene glycol, polybutylene glycol;Examples of suitable salts include, but are not limited to, metal salts such as calcium chloride, aluminum hydroxide, magnesium chloride, and copper sulfate;

[0013] The thickening substance of the present invention is preferably a polysaccharide or a hydrophilic polymer, and more preferably a polysaccharide, particularly a polysaccharide having a main chain with a structure in which glucose is glycosidically bonded (e.g., xanthan gum, cellulose, etc.) or a polysaccharide having a main chain with a structure in which mannose is glycosidically bonded (e.g., guar gum, locust bean gum, etc.).

[0014] The thickening substances of the present invention include substances that have a thickening effect only when combined with other ingredients. For example, some of the alcohols exemplified above have a thickening effect when combined with a polysaccharide such as tamarind gum.

[0015] The thickening substance of the present invention is preferably one that is highly safe when applied to the body, i.e., one that has little or no adverse effects on the human body. For this reason, the thickening substance of the present invention is preferably one that has a quality at least equal to or higher than that approved as a food additive. In terms of being free of impurities and safe, thickening substances such as hydrophilic polymers obtained by synthesis can be used.

[0016] When using a thickening substance derived from a natural product (e.g., polysaccharides such as xanthan gum, locust bean gum, guar gum, etc.) as the thickening substance of the present invention, there is a large variation in physical properties between manufacturers and lots, so it is preferable to prepare the viscoelastic composition of the present invention by changing the concentration (e.g., weight %) by a method such as adding water as a dispersion medium while checking the shear storage modulus and other desired physical property values ​​themselves.

[0017] When a combination of two or more components is used as the thickening substance of the present invention, a viscoelastic composition having desired physical properties can be obtained by changing the mixing ratio of the two or more components. When a combination of two or more components is used as the thickening substance of the present invention, it is preferable that one of the components contains a polysaccharide. Examples of such polysaccharides include polysaccharides having a main chain with a structure in which glucose is glycosidically bonded, or polysaccharides having a main chain with a structure in which mannose is glycosidically bonded. Examples of polysaccharides having a main chain with a structure in which glucose is glycosidically bonded include xanthan gum and cellulose, and the mixing ratio of polysaccharides having a main chain with a structure in which glucose is glycosidically bonded (weight % of the polysaccharide in the entire thickening substance) is preferably 5 to 90% by weight, more preferably 10 to 80% by weight, and even more preferably 20 to 70% by weight. On the other hand, examples of polysaccharides having a main chain formed by glycosidic bonds between mannose include guar gum and locust bean gum, and the mixing ratio of polysaccharides having a main chain formed by glycosidic bonds between mannose (weight % of said polysaccharide in the entire thickening substance) is preferably 10 to 90 weight %, more preferably 20 to 85 weight %, and even more preferably 30 to 80 weight %. When a combination of two or more kinds of components is used as the thickening substance of the present invention, the two or more kinds of components are preferably a combination of two kinds of polysaccharides. The combination of two kinds of polysaccharides can preferably be a combination of a polysaccharide having a main chain with a structure in which glucose is glycosidically bonded and a polysaccharide having a main chain with a structure in which mannose is glycosidically bonded, for example, a combination of xanthan gum and guar gum, or a combination of xanthan gum and locust bean gum. The weight ratio of the combination can be appropriately determined while confirming that the desired physical property values ​​such as the shear storage modulus can be obtained, but preferably, the weight ratio of the polysaccharide having a main chain with a structure in which glucose is glycosidically bonded to the polysaccharide having a main chain with a structure in which mannose is glycosidically bonded is 5:95 to 90:10, more preferably 10:90 to 80:20, and even more preferably 20:80 to 70:30. In addition, even when a combination of two or more components is used as the thickening substance of the present invention, it is preferable to prepare the viscoelastic composition of the present invention by changing the concentration (e.g., weight %) by a method such as adding water, which is a dispersion medium, while checking the shear storage modulus and other desired physical properties themselves, as described above.

[0018] The "water" used in the viscoelastic composition of the present invention is not particularly limited, but includes soft water, pure water, ultrapure water, deionized water, distilled water, tap water, etc., and may be a physiological aqueous solution such as physiological saline, Ringer's solution, or acetated Ringer's solution.

[0019] The viscoelastic composition of the present invention has a shear storage modulus G' of 0.7 Pa or more. In one embodiment of the present invention, the shear storage modulus G' of the viscoelastic composition of the present invention is defined as a numerical value measured at room temperature, particularly at 25°C. The viscoelastic composition of the present invention is used for securing a visual field of an endoscope, and a typical mode of use in such use is that the viscoelastic composition is fed from the proximal end of the endoscope through a forceps channel to the distal end of the endoscope, and then released into the inside of the tube, and physically pushes aside liquids such as blood, intestinal juice, and bile, and semi-solids such as food residues and excrement, for a certain period of time. In such a mode of use, the viscoelastic composition of the present invention is fed from the proximal end of the endoscope to the distal end, and then acts in the body for a short period of time, usually only a few minutes at most, and the temperature of the viscoelastic composition, which is usually stored and injected at room temperature (particularly 25°C), is not expected to change significantly during its action. Furthermore, even if the residence time of the viscoelastic composition of the present invention inside the tube becomes long for some reason, the temperature rises, the physical properties change, and as a result, it becomes difficult to ensure the desired field of view, the temperature of the viscoelastic composition near the tip of the endoscope, which is the observation area, always remains near room temperature (particularly, 25° C.) by additionally injecting the viscoelastic composition of the present invention that is indwelled at room temperature (particularly, 25° C.). Therefore, it is reasonable to specify the shear storage modulus G' of the viscoelastic composition of the present invention as a value measured at room temperature, particularly at 25° C.

[0020] The shear storage modulus G' can be measured using any rheometer, for example, HAAKE MARSIII manufactured by Thermo Fisher Scientific Co., Ltd. In one embodiment of the present invention, the shear storage modulus G' of the viscoelastic composition of the present invention is measured under the following measurement conditions: measurement temperature: 25.0°C, gap: 1.000 mm, stress: 1000 mPa, frequency: 0.5000 Hz, and is measured as a value 30 minutes after the start of the measurement.

[0021] In one embodiment of the present invention, the shear storage modulus G' of the viscoelastic composition of the present invention is 0.7 Pa or more, 0.75 Pa or more, 0.8 Pa or more, 0.85 Pa or more, 0.9 Pa or more, 0.95 Pa or more, 1.0 Pa or more, 1.05 Pa or more, 1.1 Pa or more, 1.15 Pa or more, 1.2 Pa or more, 1.25 Pa or more, 1.3 Pa or more, 1.35 Pa or more, 1.4 Pa or more, 1.45 Pa or more, 1.5 Pa or more, 1.55 Pa or more, 1.6 Pa or more or above, 1.65 Pa or more, 1.7 Pa or more, 1.75 Pa or more, 1.8 Pa or more, 1.85 Pa or more, 1.9 Pa or more, 1.95 Pa or more, 2.0 Pa or more, 2.1 Pa or more, 2.2 Pa or more, 2.3 Pa or more, 2.4 Pa or more, 2.5 Pa or more, 2.6 Pa or more, 2.7 Pa or more, 2.8 Pa or more, 2.9 Pa or more, 3.0 Pa or more, 3.1 Pa or more, 3.2 Pa or more, 3.3 Pa or more, 3.4 Pa or more, or 3.5 Pa or more.

[0022] In one embodiment of the invention, the shear storage modulus G' of the viscoelastic composition of the invention is 7.0 Pa or less, 6.5 Pa or less, 6.0 Pa or less, 5.5 Pa or less, 5.0 Pa or less, 4.5 Pa or less, 4.0 Pa or less, 3.5 Pa or less, or 3.0 Pa or less.

[0023] In one embodiment of the present invention, the shear storage modulus G' of the viscoelastic composition of the present invention is 0.7 to 7.0 Pa, 0.7 to 6.5 Pa, 0.7 to 6.0 Pa, 0.7 to 5.5 Pa, 0.7 to 5.0 Pa, 0.7 to 4.5 Pa, 0.7 to 4.0 Pa, 0.7 to 3.5 Pa, or 0.7 to 3.0 Pa. In another embodiment of the present invention, the shear storage modulus G' of the viscoelastic composition of the present invention is 0.75 to 7.0 Pa, 0.75 to 6.5 Pa, 0.75 to 6.0 Pa, 0.7 In still another embodiment of the present invention, the shear storage modulus G' of the viscoelastic composition of the present invention is 0.8 to 7.0 Pa, 0.8 to 6.5 Pa, 0.8 to 6.0 Pa, 0.8 to 5.5 Pa, 0.8 to 5.0 Pa, 0.8 to 4.5 Pa, 0.8 to 4.0 Pa, 0.8 to 3.5 Pa, or 0.75 to 3.0 Pa.

[0024] If the shear storage modulus G' of the viscoelastic composition is 0.7 Pa or more, when the viscoelastic composition is injected into the inside of a tube through a channel of an endoscope, the elastic component of the composition can physically push aside liquids such as blood, intestinal juice, and bile, and semi-solids such as food residue and excrement, and the elastic component of the composition is difficult to mix with the liquids and semi-solids, so that the liquids and semi-solids that have been physically pushed aside once can be prevented from returning to the field of view in a short time due to diffusion or suspension, and when there is persistent bleeding in or around the field of view of the endoscope and the blood is released into the composition filling the lumen, the composition can prevent the blood from diffusing and suspending in a short time inside the composition, and as a result, a clear field of view can be maintained for a relatively long time. The higher the shear storage modulus G' of the viscoelastic composition of the present invention is above 0.7 Pa, the more remarkable the property of physically pushing aside the liquids and semi-solids and the property of being difficult to mix with the liquids and semi-solids. On the other hand, if the shear storage modulus G' of the viscoelastic composition is smaller than 0.7 Pa, it is difficult to physically push aside liquids or semisolids inside the tube, and even if it is possible to push them aside, the composition is likely to mix with the liquids or semisolids, so that the liquids or semisolids return to the field of view in a short time due to diffusion or suspension, or if there is persistent bleeding in or around the field of view of the endoscope and the blood is released into the composition filling the lumen, the blood diffuses and suspends inside the composition in a short time, resulting in an inability to maintain a clear field of view. In addition, when the viscoelastic composition of the present invention is injected into an application site through a forceps channel (inner diameter of about 2.0 to 3.8 mm), particularly when the viscoelastic composition is injected into an application site through a forceps channel with a treatment tool such as forceps inserted therein, a viscoelastic composition having a lower shear storage modulus G' is preferable from the viewpoint of improving the channel passability of the viscoelastic composition. From this viewpoint, the shear storage modulus G' of the viscoelastic composition of the present invention is preferably not more than 7.0 Pa, more preferably not more than 6.5 Pa, and even more preferably not more than 6.0 Pa. Taking these into consideration, it is preferable to select an optimal shear storage modulus G' depending on the purpose of use of the viscoelastic composition of the present invention, the site to which the endoscope in which the viscoelastic composition of the present invention is used is applied, and the like.

[0025] In one embodiment of the present invention, the viscoelastic composition of the present invention has a loss tangent (tan δ) greater than 0.6. The "loss tangent" is defined as the shear loss modulus G" divided by the shear storage modulus G' as follows: [ka]

[0026] In one embodiment of the present invention, the loss tangent of the viscoelastic composition of the present invention is defined as the value measured at room temperature, in particular at 25°C.

[0027] The loss tangent can be measured using any rheometer, for example, HAAKE MARSIII manufactured by Thermo Fisher Scientific Co., Ltd. In one embodiment of the present invention, the loss tangent of the viscoelastic composition of the present invention is measured under the following measurement conditions: measurement temperature: 25.0° C., gap: 1.000 mm, stress: 1000 mPa, frequency: 0.5000 Hz, and is measured as a value 30 minutes after the start of the measurement.

[0028] In one embodiment of the present invention, the loss tangent of the viscoelastic composition of the present invention is 3.0 or less, 2.9 or less, 2.8 or less, 2.7 or less, 2.6 or less, 2.5 or less, 2.4 or less, 2.3 or less, 2.2 or less, 2.1 or less, 2.0 or less, 1.9 or less, 1.8 or less, 1.7 or less, 1.6 or less, 1.5 or less, 1.4 or less, 1.3 or less, 1.2 or less, 1.1 or less, 1.0 or less, 0.95 or less, 0.9 or less, 0.85 or less, 0.8 or less, 0.75 or less, 0.7 or less, or 0.65 or less.

[0029] In one embodiment of the present invention, the loss tangent of the viscoelastic composition of the present invention is 0.65 or more, 0.7 or more, 0.75 or more, 0.8 or more, 0.85 or more, 0.9 or more, 0.95 or more, or 1.0 or more.

[0030] The viscoelastic composition of the present invention may contain additional components such as a dispersant for dispersing the thickening substance in water and an osmotic pressure regulator. The dispersant makes it possible to prevent lumps from forming when dispersing the thickening substance in water and / or to shorten the time required to disperse the thickening substance in water. The osmotic pressure regulator arbitrarily adjusts the osmotic pressure of the viscoelastic composition of the present invention, and preferably, the osmotic pressure regulator adjusts the osmotic pressure of the viscoelastic composition of the present invention to approximately the same level as that of physiological saline (for example, 0.6 to 1.8, preferably 0.7 to 1.5, more preferably 0.8 to 1.2 as the osmotic pressure ratio with physiological saline). Any substance having the above-mentioned action can be used as the dispersant or osmotic pressure regulator of the present invention, and a single substance (for example, glycerin) can be used as the dispersant and osmotic pressure regulator of the present invention.

[0031] Furthermore, the viscoelastic composition of the present invention may contain additives such as preservatives and antiseptics.

[0032] As described in International Publication No. WO 2017 / 057504 (Patent Document 1, the entire text of which is incorporated herein by reference), by setting the hardness and viscosity of the viscoelastic composition to a predetermined value, it is possible to improve the channel passability when the viscoelastic composition is injected into an application site through a channel of an endoscope (e.g., a forceps channel). From this viewpoint, in one embodiment of the present invention, the viscoelastic composition of the present invention has a hardness of 550 N / m 2 Less than 400N / m 2 In a further embodiment of the present invention, the viscoelastic composition of the present invention may have a hardness of 550 N / m or less at room temperature, in particular at 25° C., and / or a viscosity of 500 to 1500 mPa·s. 2 Less than 400N / m 2 and / or may have a viscosity at room temperature, in particular at 25° C., of 200 to 2000 mPa·s, preferably 500 to 1500 mPa·s.

[0033] Hardness can be measured using any creep meter. For example, hardness can be measured using a creep meter Model RE2-33005C manufactured by Yamaden Co., Ltd., by filling a stainless steel petri dish (outer diameter 45 mm, inner diameter 41 mm, outer dimensions 18 mm, inner dimensions 15 mm) with a specimen adjusted to 25°C, aligning the specimen surface to the same height as the petri dish, and measuring the following conditions: storage pitch: 0.02 sec, measurement strain rate: 66.67%, measurement speed: 10 mm / sec, return distance: 5.00 mm, sample thickness: 15.00 mm, contact surface: diameter 20.00 mm, contact area: 0.000 mm 2 The measurement can be performed using a plunger (Yamaden Co., Ltd., shape: disk, model: P-56, description: φ20 × t 8) under the above conditions.

[0034] The viscosity can be measured using any rheometer. For example, the viscosity can be determined by using a rheometer HAAKE MARSIII manufactured by Thermo Fisher Scientific Co., Ltd., placing about 1 mL of a sample on the lower plate (Unltere Plate TMP35), and measuring using a sensor (Platte P35 Til) under the conditions of measurement temperature: 25.0°C, gap: 1.000 mm, stress: 1000 mPa, and frequency: 0.5000 Hz or less, and measuring the value 30 minutes after the start of measurement.

[0035] Also, as described in International Publication No. 2017 / 057504 (Patent Document 1), by setting the electrical conductivity of the viscoelastic composition to a predetermined value, a viscoelastic composition suitable for endoscopic treatment (particularly, electrical treatment such as electrical cutting or electrical coagulation) can be obtained. From this viewpoint, in one aspect of the present invention, the viscoelastic composition of the present invention can have an electrical conductivity of 250 μS / cm or less, preferably 200 μS / cm or less. In a further aspect of the present invention, the viscoelastic composition of the present invention can have an electrical conductivity of 250 μS / cm or less, preferably 200 μS / cm or less at room temperature, particularly at 25° C.

[0036] The electrical conductivity can be measured using any electrical conductivity meter. For example, the electrical conductivity can be measured using an electrical conductivity meter CM-41X and a low electrical conductivity cell CT-57101C manufactured by Toa DKK Corporation at a measurement temperature of 25°C.

[0037] Since the viscoelastic composition of the present invention is intended to be applied to the body of an animal (human), it is preferable that the composition is sterilized before application. For example, the viscoelastic composition of the present invention is preferably sterilized under the conditions of 121°C and 15 minutes (Fo value control: Fo=20). Note that some viscoelastic compositions change their physical properties at high temperatures, so when sterilizing, it is preferable to design the material so as to achieve the desired physical properties after sterilization, or to select a material whose physical properties change little at high temperatures.

[0038] The object of the present invention is to provide a viscoelastic composition suitable for use in securing an endoscopic field of view, and a method for securing an endoscopic field of view using the viscoelastic composition; more specifically, to provide a viscoelastic composition suitable for use in securing an endoscopic field of view by pushing aside opaque dark-colored liquids or semi-solid materials that accumulate inside a tube and obstruct the endoscopic field of view, or for use in securing an endoscopic field of view when the endoscopic field of view is obstructed by persistent bleeding inside a tube, and a method for securing an endoscopic field of view using the viscoelastic composition. It is believed that the causes of obstruction of the endoscopic field of view are liquids such as blood, intestinal fluid, and bile, and semi-solid materials such as food residue and excrement, 1) accumulating within the lumen, 2) mixing with water and impairing transparency, or 3) flowing or diffusing when water is supplied. In order to ensure a good field of vision, a transparent composition having a different viscoelasticity from that of the liquid or semi-solid matter is injected into the lumen, which physically pushes them aside and removes them, thereby creating space and preventing the liquid or semi-solid matter from mixing with the liquid or semi-solid matter in a short period of time, which would result in a loss of transparency, and further making it possible to suppress the flow or diffusion of the liquid or semi-solid matter.

[0039] The viscoelastic composition of the present invention can be obtained by mixing a thickening substance with water, specifically, by combining two or more of the thickening substances, or by dissolving one type of thickening substance in water or the like and adding elasticity by performing a heat treatment. The viscoelastic composition of the present invention is preferably substantially free of air bubbles, since air bubbles in the composition would block the field of view. The term "substantially free of air bubbles" used herein means that there are no air bubbles of an amount or size that would make observation or work within the field of view of the endoscope substantially impossible, and for example, means that air bubbles cannot be seen when the viscoelastic composition is observed with the naked eye. In addition, in order to accurately observe the field of view of the endoscope, the viscoelastic composition of the present invention is preferably colorless and transparent. The term "colorless and transparent" used herein means that the composition is not colored and opaque to such an extent that observation or work within the field of view of the endoscope is substantially impossible, and for example, means that the absorbance at a light path length of 10 mm at a visible wavelength of 400 to 800 nm is 80% or less.

[0040] The viscoelastic composition of the present invention is a viscoelastic composition for securing a visual field through an endoscope, and the term "endoscope" includes endoscopes for all applications. In one embodiment of the present invention, the endoscope is a medical endoscope.

[0041] The method for ensuring a visual field of an endoscope of the present invention includes feeding the viscoelastic composition of the present invention from the proximal end of the endoscope through a channel to the tip of the endoscope. In one embodiment of the present invention, the method for ensuring a visual field of an endoscope of the present invention includes feeding the viscoelastic composition of the present invention from the proximal end of the endoscope through a forceps channel (inner diameter of about 2.0 to 3.8 mm) to the tip of the endoscope, particularly through the forceps channel with a treatment tool such as forceps inserted therein.

[0042] In the method for obtaining a visual field with an endoscope of the present invention, the term "endoscope" includes endoscopes of all uses. In one embodiment of the present invention, the endoscope is a medical endoscope.

[0043] Fig. 1 is a photograph of the proximal portion of a medical endoscope as a representative example of an endoscope. The proximal portion of the medical endoscope is equipped with a dial 11 for angle adjustment, a scope connector portion 12 for transmitting light from a light source device and image information to an electronic endoscope processor, and a forceps port 15 for inserting treatment tools such as forceps and sending them to the tip portion 1. A forceps channel that communicates from the forceps port to the tip portion, a water supply tube for water washing the lens at the tip portion, an optical system, and the like are provided in an endoscope flexible tube 17. A forceps plug 16 is attached to the forceps port 15 of the medical endoscope shown in Fig. 1. One end of a tube 13 is connected to the forceps plug 16, and the other end of the tube is connected to a connector 14 for attaching a syringe or the like. There is a valve inside the forceps plug 16, and one end of the tube 13 opens into the wall surface of the valve inside the forceps plug 16 on the forceps port 15 side. Even when a treatment tool such as forceps is inserted, the valve prevents the liquid sent through the tube from leaking out (for example, see Specific Patent Publication No. 2014-155677). EXAMPLES

[0044] Reference example An endoscope can be inserted into the digestive tract, such as the rectum, to observe the inside of the digestive tract. If there is bleeding in the digestive tract 4, blood 3 accumulates in the digestive tract, making it impossible to observe the bleeding site 2 (Fig. 2A). In such a case, a syringe is filled with tap water, and water is sent from the opening of the endoscope tip 1 through the tube 13, the forceps port 15, and the forceps channel into the digestive tract, in an attempt to wash away the accumulated blood with water. However, the accumulated blood and the sent water mixed and became suspended, turning into murky water 3". When murky water 3" accumulates in the digestive tract, the view of the endoscope is blocked by the murky water 3", making it impossible to observe the bleeding site 2 and to continue the procedure (Figs. 2B and 3). Furthermore, according to the viscoelastic composition of the present invention, when a bleeding site 2 occurs in the digestive tract 4 as shown in Figures 4A and 4B, by injecting this viscoelastic composition from the tip of the endoscope, blood 3 that has accumulated in the digestive tract is pushed aside (blood 3').Furthermore, as shown in Figure 5, the blood and the viscoelastic composition do not mix, and the boundary between them is clearly visible, making it possible to observe the bleeding site 2.

[0045] Examples and Comparative Examples In the present Examples and Comparative Examples, the relationship between the viscoelastic properties (particularly the shear storage modulus G' and the loss tangent tan δ) of the viscoelastic composition used in an endoscope and securing a visual field during endoscopic operation was examined.

[0046] The following describes a method for preparing a viscoelastic composition sample, a method for measuring physical properties related to viscoelastic characteristics, and a method for evaluating the viscoelastic composition from the viewpoint of ensuring a visual field when used in an endoscope.

[0047] (1) Sample preparation method Using a Disper (Primix Corporation) attached to TKROBOMICS No. 071093 (Primix Corporation), glycerin in an amount to a final concentration of 2.4% by weight was stirred at 1400 rpm, while raw materials xanthan gum (XG: KELTROL CG-T, Lot; 7B5905K, manufacturer: Sansho Corporation) and locust bean gum (LBG: GENUGUM, Lot; SK71280, manufacturer: Sansho Corporation) were added in a weight ratio such that the weight ratio of XG / LBG was 2 / 8, and dispersed for 2 minutes. The dispersion was added to water heated to 70°C or higher, and the container containing the dispersion was washed, and then the dispersion was stirred for 5 minutes at 5000 rpm using a Disper. After stirring, the weight was adjusted by adding water appropriately, and various XG / LBG (2 / 8) samples having the desired concentration (wt%) were prepared by stirring for 2 minutes at 3000 rpm using a Disper.

[0048] In addition, XG / LBG (5 / 5), XG / LBG (6 / 4), and XG / LBG (8 / 2) samples with the desired concentrations (wt%) were prepared in the same manner as above, except that the weight ratio of XG / LBG was 5 / 5, 6 / 4, and 8 / 2.

[0049] Furthermore, various XG / GG (7 / 3) samples with the desired concentration (wt%) were prepared in the same manner as above, except that xanthan gum (XG: Bistop D-3000C, Lot; 160523-01, manufacturer: San-Ei Gen F.F.I. Co., Ltd.) and guar gum (GG: RG100, Lot; 7091521, manufacturer: San-Ei Gen F.F.I. Co., Ltd.) were added as raw materials in a weight ratio such that the weight ratio of XG / GG was 7 / 3.

[0050] Each specimen was sterilized at 121°C for 15 minutes (Fo value control: Fo = 20) and then used in the subsequent tests.

[0051] (2) Measurement method of viscoelastic properties (G', G'' and tan δ) Measurement was performed using a rheometer HAAKE MARSIII (Thermo Fisher Scientific Co., Ltd.). After adjusting the temperature in the laboratory to 25°C, a viscoelastic composition sample (about 1 mL) adjusted to 25°C was placed on a lower plate (Unltere Plate TMP35) and measured using a sensor (Platte P35 Til) (measurement conditions: measurement temperature: 25.0°C, gap: 1.000 mm, stress: 1000 mPa, frequency: 0.5000 Hz), and the value was measured 30 minutes after the start of the measurement.

[0052] (3) Evaluation method for securing visual field The vinyl tube method described below was used as a method for evaluating the securing of the visual field. In this method, a flexible and transparent plastic tube, such as a thin polyethylene packaging bag, was used as the digestive tract, and the tip of the Surflow indwelling needle inserted from the outside to the inside of the plastic tube was used as the bleeding site inside the digestive tract, simulating the actual endoscope application environment. In a laboratory set at a room temperature of 23°C, the tip of the Surflow indwelling needle was inserted from the outside to the inside of a plastic tube (ELPA, MH-CT11H packaging bag) with a width of about 4.2 cm in a flat state (therefore, the cross-sectional diameter when completely filled with liquid is about 2.6 to 2.7 cm), so that the needle was parallel to the longitudinal direction of the plastic tube, and the indwelling needle was fixed to the plastic tube, and an extension tube X2-100 (Top Corporation) was connected to the other end of the indwelling needle, and further, the distal part of the soft tube of an endoscope GIF-Q260J (Olympus Corporation) was inserted into the plastic tube. At this time, the tip of the Surflo indwelling needle was arranged so that the insertion direction of the distal part of the flexible tube of the endoscope was opposite to that of the distal part of the flexible tube of the endoscope, and the distance between the tip of the Surflo indwelling needle and the distal part of the flexible tube of the endoscope was about 3 to 6 cm. Then, by placing fixtures under both ends near the center of the plastic tube (a part about 10 cm away, including the part where the tip of the indwelling needle is fixed and the part where the distal part of the flexible tube of the endoscope is inserted), a slope was created so that the initially introduced blood would stay near the center. Then, 50 mL of pig blood was injected into the plastic tube, and after confirming that the blood had accumulated near the center of the plastic tube, the extension tube connected to the indwelling needle was connected to a silicone tube L / S14 (Cole-Parmer Instrument Co.) connected to a pump MasterFlex L / S 07522-30 type (Cole-Parmer Instrument Co.). Using the pump, pig blood was continuously injected into a plastic tube via a silicone tube, an extension tube, and an indwelling needle (pump settings: fixed-time supply mode, flow rate: 10 mL / min, on / off: 1 sec / 1 sec, batch number: 9999).The continuous injection of pig blood into the plastic tube imitated bleeding inside a tube such as the digestive tract, but the injection speed was set to be faster than the generally assumed bleeding speed to set a more severe mimicking environment. After filling a 50 mL syringe (JMS) with a viscoelastic composition sample whose temperature was adjusted to 25°C, one end of an irrigator (BioShield irrigator (HZ-711133), US endoscopy) was connected to the syringe, and the other end of the irrigator was connected to the connector of the endoscope. The viscoelastic composition sample was continuously injected into the plastic tube through the forceps channel at an injection speed of about 0.5 to 5 mL / s by operating the syringe, and the visual field securing performance was evaluated. The performance of securing the visual field was evaluated comprehensively from the viewpoints of securing a physical transparent space (whether or not sufficient transparent space can be secured by pushing aside blood (suppressing the flow and diffusion of blood) when the sample is injected) and maintaining transparency (whether or not transparency can be maintained even when the injection of the sample is interrupted). If the injection of the sample enabled observation inside the plastic tube (observation of the tip of the Surflow indwelling needle), it was judged as "passed", and if it was difficult to observe inside the plastic tube, it was judged as "failed". For example, if it was necessary to inject a large amount of sample to secure a physical transparent space, or if the blood quickly became wet in the sample when the injection of the sample was interrupted, and transparency was lost, it was judged as "failed". In addition, if the performance of securing the visual field was "passed", the visibility of the needle tip was also evaluated. Specifically, if the tip of the Surflow indwelling needle was visible, it was judged as "+", and if the tip of the Surflow indwelling needle was clearly visible, it was judged as "++".

[0053] (4) Method for evaluating channel passivity In a laboratory set to a room temperature of 23°C, a 50 mL syringe (JMS Co., Ltd.) was filled with a viscoelastic composition sample adjusted to 25°C, and a catheter tube (inner diameter 3 mm, length 1000 mm) simulating the inner diameter of an endoscope's forceps port was attached to the tip of the syringe, and the passability of the viscoelastic composition sample was subjectively evaluated. If it passed smoothly, it was rated as "++", if there was some resistance but within the practically acceptable range, it was rated as "+", and if there was too much resistance to withstand practical use or too much resistance to pass, it was rated as "-".

[0054] [Test Example] Relationship between the viscoelastic properties (G' and tan δ) of the viscoelastic composition used in an endoscope and securing the visual field in the endoscope Viscoelastic composition samples with different viscoelastic properties were prepared, and the performance of securing the visual field for each sample was judged to be pass or fail, and the relationship with each viscoelastic property was evaluated. The test results were as follows.

[0055] [Table 1]

[0056] From these results, it was demonstrated that, regardless of the raw materials of the viscoelastic composition samples, all samples with a shear storage modulus G' of 0.7 Pa or more have the desired visibility. It was also demonstrated that even if the loss tangent of the sample is higher than 0.6, the desired visibility can be achieved as long as the shear storage modulus G' is 0.7 Pa or more.

[0057] [Test Example] Relationship between the viscoelastic properties (G' and tan δ) of the viscoelastic composition used in endoscopes and channel passability Viscoelastic composition samples with different viscoelastic properties were prepared, and the channel passability of each sample was determined and the relationship with each viscoelastic property was evaluated. The test results were as follows.

[0058] [Table 2]

[0059] This result demonstrates that, from the viewpoint of channel passability, a viscoelastic composition having a lower shear storage modulus G' is preferred. [Explanation of symbols]

[0060] 1 Endoscope tip 2 Bleeding site 3, 3' blood 3” Muddy water 4 Gastrointestinal tract 5 Viscoelastic composition 11 Dial 12 Scope connector 13 Tube 14 Connectors 15 Forceps port 16 Forceps plug 17 Endoscope flexible tube

Claims

1. A viscoelastic composition for ensuring the visual field of an endoscope by being fed into the vicinity of the tip of the endoscope, which is the observation area, said viscoelastic composition containing a viscosity-increasing substance and water, having a shear storage modulus G' of 0.7 Pa or more and a loss tangent of greater than 0.

6.

2. The viscoelastic composition according to claim 1 , wherein the thickening substance is a polysaccharide or a hydrophilic polymer.

3. The viscoelastic composition according to claim 1 or 2, wherein the viscoelastic composition is colorless and transparent.

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