Lubricant for inserting endoscope into small intestine

Abstract

To provide a lubricant for inserting an endoscope into a small intestine, the lubricant enabling alleviation of pain and reduced invasion at the time of insertion of the endoscope into the small intestine.SOLUTION: Provided is a lubricant for inserting an endoscope into a small intestine, the lubricant having viscosity at 25°C and a shearing speed of 100 s-1 of 0.008 to 0.302 Pa s.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a lubricant for use in inserting a small intestine endoscope. [Background technology]

[0002] Device assisted enteroscopy is an extremely important examination for detecting organic abnormalities in the small intestine (tumorous disease, inflammatory disease, etc.). Device assisted enteroscopy includes two types of balloon assisted endoscopy: single-balloon endoscopy (SBE) using a single balloon endoscope and double-balloon endoscopy (DBE) using a double balloon endoscope.

[0003] Small intestinal endoscopy allows observation while cleaning the inside of the intestine, has high diagnostic accuracy, and allows treatment as well as observation. However, small intestinal endoscopy is more likely to cause pain during endoscope insertion, pancreatitis, gastrointestinal perforation, and other complications than general upper gastrointestinal endoscopy of the esophagus, stomach, etc., or lower gastrointestinal endoscopy of the large intestine, etc., and is often performed while the patient is hospitalized, as it is a relatively invasive examination. In addition, it has been reported that the completion rate of upper and lower gastrointestinal endoscopy is very high at about 95 to 100%, while the completion rate of small intestinal endoscopy is low at about 50% (see Non-Patent Document 1). Therefore, capsule endoscopy has been developed and introduced as an alternative examination method.

[0004] Although capsule endoscopy is less invasive than balloon endoscopy, it has many limitations, such as being limited to observation and not being able to perform treatment, and not being able to be performed on patients with intestinal obstruction, etc. It is hoped that by reducing the invasiveness of small intestinal endoscopy, for example by reducing pain, suppressing the occurrence of complications, and increasing the completion rate, the indications for small intestinal endoscopy will expand.

[0005] In small intestinal endoscopy, when an endoscope is inserted from the anus through the large intestine to the small intestine, or when an endoscope is inserted from the mouth side through the esophagus and stomach to the small intestine, it is necessary to cross multiple small intestinal bends 10, as shown in FIG. 1. At that time, a load (weight) is applied from the endoscope shaft 12 to the intestinal wall at the bends 10, which leads to pain and complications (pancreatitis, digestive tract perforation, etc.). This is the main reason why small intestinal endoscopy is highly invasive and has a low success rate. In order to facilitate the insertion of the endoscope into the body, the endoscope shaft 12 may be surrounded by an overtube made of resin or the like, but a load (weight) is still applied to the intestinal wall at the bends 10.

[0006] For example, as shown in Fig. 2(a), the load applied from the endoscope shaft 12 or overtube 18 to the intestinal wall 14 of the small intestine is thought to depend on the friction between the endoscope shaft 12 or overtube 18 and the mucosal surface of the intestinal wall 14 of the small intestine. If the kinetic friction coefficient between the endoscope shaft 12 or overtube 18 and the intestinal wall 14 is high, the force received by the intestinal wall 14 increases, resulting in greater pain and invasiveness. Reducing the friction between the endoscope shaft 12 or overtube 18 and the intestinal wall 14 can be an effective means of reducing the load (weight) on the intestinal wall 14 when the endoscope is inserted, thereby reducing pain and invasiveness.

[0007] One possible method for reducing this friction is to apply a lubricant to the inside of the small intestine. For example, as shown in Fig. 2(b), if a lubricant 16 is applied to the intestinal wall 14 to lower the coefficient of dynamic friction between the endoscope shaft 12 or overtube 18 and the intestinal wall 14, the load (weight) received by the intestinal wall 14 will be reduced, which is thought to reduce pain and invasiveness.

[0008] However, currently, only the application of a gel-like lubricant to the anal area is standardized during endoscopic examination, and the application of lubricant to the intestinal tract during small intestinal endoscopy has not been standardized.

[0009] Patent Documents 1 to 3 describe viscoelastic compositions for securing an endoscopic field of view, which contain a thickening substance and water. However, as described in the following paragraphs, "The object of the present invention is to provide a viscoelastic composition which is suitable for securing an endoscopic field of view by pushing aside an opaque dark-colored liquid that accumulates inside a tube and obstructs the endoscopic field of view, and which has excellent operability, and a method for securing an endoscopic field of view using such a viscoelastic composition. It is also desirable to provide a viscoelastic composition which can assist in simple hemostatic treatment" (paragraph 0005 of Patent Document 1), and "The object of the present invention is to provide a viscoelastic composition which is suitable for securing an endoscopic field of view, and a method for securing an endoscopic field of view using such a viscoelastic composition" (paragraph 0006 of Patent Documents 2 and 3), there is no mention or consideration of reducing friction between the endoscope shaft or overtube and the intestinal wall of the small intestine.

[0010] Furthermore, Patent Documents 1-3 state that the viscoelastic composition for ensuring a visual field has a predetermined viscosity, but only a wide range of viscosities and a shear storage modulus G' are specified. For example, Patent Document 1 states that "The present invention aims to provide a viscoelastic composition that is excellent in operability and can ensure a good visual field, and preferably to provide a viscoelastic composition that can assist in simple hemostatic treatment... In order to ensure a good visual field, a transparent composition having a viscoelasticity different from that of liquids such as blood, intestinal fluid, bile, and semi-solids such as excrement is injected into the lumen to physically push aside and remove these substances, thereby ensuring space, and at the same time, the composition is mixed with liquids such as blood, intestinal fluid, bile, and semi-solids such as excrement, thereby ensuring a good visual field." It is difficult to mix with semi-solid materials, and it is possible to suppress the flow and diffusion of the liquid. The objective of excellent operability means that the viscoelastic composition can be passed through the forceps port of the endoscope without excessive resistance. The objective of enabling the assistance of a simple hemostatic treatment means that the bleeding site can be confirmed in the presence of the viscoelastic composition, and that it is possible to assist in a hemostatic treatment using a high-frequency current. As described in paragraph 0015, the viscosity in Patent Documents 1-3 is specified to be "difficult to mix with semi-solid materials" for "ensuring a visual field," and to be "passed through the forceps port of the endoscope without excessive resistance" for "operability in an endoscope." The viscosity and shear storage modulus G' specified for the viscoelastic composition for securing a visual field in Patent Documents 1-3 are not values ​​that take into consideration the reduction of friction between the endoscope shaft or overtube and the intestinal wall of the small intestine.

[0011] Patent Document 4 describes an endoscope with an overtube, in which a passage for a lubricant is provided in the side wall of the tube, but does not describe any examples in which a lubricant is used.

[0012] Patent Document 5 describes a hydrophilic lubricant for endoscopes which comprises a solution containing an emulsifier having a hydrophilic group and a lipophilic group and a polar solvent, or a solution containing a hydrophilic polymer, an emulsifier having the hydrophilic group and a lipophilic group, and the polar solvent, and which is applied to the surface of the insertion part of an endoscope to impart lubricity to the surface of the insertion part in a wet state, and describes that the hydrophilic polymer comprises at least one member selected from the group consisting of polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, sodium polyacrylate, and sodium alginate, sodium carboxymethylcellulose, xanthan gum, carrageenan, pullulan, and gelatin.

[0013] Patent Document 6 describes a lubricant supplying device that supplies a lubricant for an endoscope containing water, propylene glycol, glycerin, hydroxyethyl cellulose, parabens, carbomer, or sodium bicarbonate.

[0014] Non-Patent Document 2 describes a method in which an endoscope lubricating jelly diluted with water is injected into the overtube of a double-balloon endoscope in order to facilitate the movement of the endoscope during endoscopic balloon dilation for small intestinal stenosis in Crohn's disease.

[0015] However, Patent Documents 5 and 6 and Non-Patent Document 2 do not discuss the specific viscosity of the lubricant for reducing friction between the endoscope shaft or overtube and the intestinal wall of the small intestine. [Prior art documents] [Patent documents]

[0016] [Patent Document 1] International Patent Application Publication No. 2017 / 057504 Brochure [Patent Document 2] International Patent Application Publication No. 2020 / 105668 Brochure [Patent Document 3] Patent Publication No. 2021-121318 [Patent Document 4] Patent No. 4513825 [Patent Document 5] Patent No. 3469770 [Patent Document 6] Utility Model Registration No. 3143923 [Non-patent literature]

[0017] [Non-Patent Document 1] Takano N, Gastrointest Endosc, 2011 [Non-Patent Document 2] Gastroenterological Endoscopy, Vol 60 (5), pp.1107-1115 (2017) Summary of the Invention [Problem to be solved by the invention]

[0018] An object of the present invention is to provide a lubricant for use in inserting an endoscope into the small intestine, which makes it possible to alleviate pain and reduce invasiveness when inserting an endoscope into the small intestine. [Means for solving the problem]

[0019] The present invention is a method for producing a 25°C, 100s -1 The lubricant has a shear rate viscosity in the range of 0.008 to 0.918 Pa·s.

[0020] In the lubricant for insertion into a small intestinal endoscope, the viscosity at the shear rate is preferably in the range of 0.027 to 0.069 Pa·s.

[0021] The lubricant for insertion of a small intestine endoscope preferably contains at least one of carboxymethyl cellulose, xanthan gum, hydroxyethyl cellulose, sodium alginate, and sodium polyacrylate. Effect of the Invention

[0022] The present invention can provide a lubricant for use in inserting an endoscope into the small intestine, which can alleviate pain and reduce invasiveness during insertion of an endoscope into the small intestine. [Brief description of the drawings]

[0023] [Figure 1] 1 is a schematic diagram showing the state of the intestinal wall at a bent portion of the small intestine and the shaft portion of the endoscope when the endoscope is inserted into the small intestine. FIG. [Diagram 2] 1 is a schematic diagram showing friction between an endoscope shaft portion or an overtube portion and an intestinal wall. FIG. [Diagram 3] FIG. 13 is a graph showing the relationship between the dynamic friction coefficient between an endoscope shaft and an intestinal wall and the viscosity of a lubricant based on a Stribeck curve. [Figure 4] 1 is a photograph showing a method for investigating the relationship between the dynamic friction coefficient between the digestive tract mucosa and the shaft of an endoscope, and the load (N) applied to the intestine in an embodiment. [Diagram 5] 6 is a photograph showing a method for measuring the dynamic friction coefficient between the digestive tract mucosa and the shaft portion of an endoscope in an example. [Figure 6] 1 is a graph showing the coefficient of dynamic friction between the gastrointestinal mucosa and the shaft of an endoscope, and the load (N) applied to the intestine, relative to the concentration of a thickening agent (HEC). [Figure 7] 1 is a graph showing the relationship between the dynamic friction coefficient between the digestive tract mucosa and the endoscope shaft, and the load (N) applied to the intestine. [Figure 8] 1 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the overtube portion and the small intestinal mucosa versus the concentration of carboxymethyl cellulose (CMC) in Example 1. [Figure 9] 1 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the overtube portion and the small intestinal mucosa versus the concentration of xanthan gum (XG) in Example 1. [Figure 10] 1 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the overtube portion and the small intestinal mucosa versus the concentration of hydroxyethyl cellulose (HEC) in Example 1. [Figure 11]1 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the overtube portion and the small intestinal mucosa versus the concentration of sodium alginate (SA) in Example 1. [Figure 12] 1 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the overtube portion and the small intestinal mucosa versus the concentration of sodium polyacrylate (SPA) in Example 1. [Figure 13] 1 is a graph showing the relationship between the viscosity at each shear rate (1 s-1, 10 s-1, 100 s-1, 1000 s-1) and the dynamic friction coefficient between the overtube portion and the small intestinal mucosa in Example 1. [Figure 14] 13 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the endoscope shaft and the small intestinal mucosa versus the concentration of carboxymethyl cellulose (CMC) in Example 2. [Figure 15] 13 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the endoscope shaft and the small intestinal mucosa versus the concentration of xanthan gum (XG) in Example 2. [Figure 16] 13 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the endoscope shaft and the small intestinal mucosa versus the concentration of hydroxyethyl cellulose (HEC) in Example 2. [Figure 17] 13 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the endoscope shaft and the small intestinal mucosa versus the concentration of sodium alginate (SA) in Example 2. [Figure 18] 13 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the endoscope shaft and the small intestinal mucosa versus the concentration of sodium polyacrylate (SPA) in Example 2. [Figure 19] 13 is a graph showing the relationship between the viscosity at each shear rate (1 s-1, 10 s-1, 100 s-1, 1000 s-1) and the dynamic friction coefficient between the endoscope shaft and the small intestinal mucosa in Example 2. [Figure 20] 13 is a schematic diagram showing how the endoscope shaft portion inserted into the inner cavity of the overtube portion is subjected to reciprocal motion in Example 3. FIG. [Figure 21]13 is a graph showing the change over time in the dynamic friction coefficient between the endoscope shaft and the overtube due to repetitive motion in Example 3 (load 100 g). [Figure 22] 13 is a photograph showing a portion of the inner surface of the overtube where a hydrophilic coating is present (upper portion) and a portion where the hydrophilic coating has fallen off (lower portion) in Example 3. [Diagram 23] 13 is a graph showing the viscosity (Pa·s) and the dynamic friction coefficient between the endoscope shaft and the overtube versus the concentration of sodium polyacrylate (SPA) in Example 3. [Figure 24] 13 is a graph showing the relationship between the viscosity at each shear rate (1 s-1, 10 s-1, 100 s-1, 1000 s-1) and the dynamic friction coefficient between the endoscope shaft portion and the overtube portion in Example 3. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The following describes an embodiment of the present invention. The embodiment is merely an example of implementing the present invention, and the present invention is not limited to the embodiment.

[0025] The lubricant for inserting a small intestinal endoscope according to the embodiment of the present invention is -1 The viscosity of the lubricant at a shear rate of 25°C for 100s is in the range of 0.008 to 0.918 Pa s. -1 The viscosity at this shear rate is preferably in the range of 0.008 to 0.302 Pa·s, and more preferably in the range of 0.027 to 0.069 Pa·s.

[0026] As described above, reducing the friction between the endoscope shaft or overtube and the intestinal wall of the small intestine (small intestinal mucosal surface) can be an effective means of reducing the load (weight) on the small intestinal wall when inserting an enteroscope. However, it is very difficult to measure this friction in vivo, and it is also very difficult to obtain a sufficient amount of excess small intestine specimen from a patient undergoing surgery and measure it ex vivo. Therefore, measuring this friction is extremely difficult, and no research has been done on the lubrication between the endoscope shaft or overtube and the small intestinal mucosal surface until now.

[0027] Therefore, the inventors constructed a friction measurement model using small intestines collected from cadavers donated to forensic autopsies. Because the cadavers were donated to forensic autopsies, many human small intestine specimens could be obtained stably, and highly reproducible repeated experiments and evaluations were realized by mass-producing high-quality friction evaluation models. Furthermore, small intestinal endoscopic examinations often take a long time, and as the examination time increases, the resistance when the endoscope passes through the overtube increases, which has a negative effect on the progress of the examination (for example, an extension of the total examination time). Therefore, the inventors also evaluated the friction between the endoscope shaft and the overtube.

[0028] The inventors have studied the reduction of friction between the endoscope shaft or overtube and the small intestinal mucosal surface, constructed the above-mentioned friction measurement model, analyzed the relationship between the physical properties (viscosity) of the lubricant and the dynamic friction coefficient as shown below, identified the ideal physical properties (viscosity) of the lubricant that minimizes the dynamic friction coefficient between the endoscope shaft or overtube and the small intestinal mucosal surface, and developed a new lubricant. This ideal lubricant can reduce the pain and incidence of complications during small intestinal endoscopic examination, and contribute to improving the medical level of small intestinal diseases.

[0029] Details will be explained in the Examples section, but first, we discovered that a lower coefficient of dynamic friction between the gastrointestinal mucosa and the endoscope shaft reduces the burden on the gastrointestinal wall. Therefore, we changed the concentration of various thickeners relative to water to identify the concentration range that minimizes the coefficient of dynamic friction.

[0030] Tribology is the science that deals with friction and lubrication, and is applied in various medical fields. In the boundary lubrication and mixed lubrication phases, the coefficient of friction decreases as the viscosity of the lubricant increases, the speed increases, and the load decreases, but in the hydrodynamic lubrication phase, the coefficient of friction begins to increase. This behavior of the coefficient of friction is conceptually represented as a Stribeck curve. From the perspective of tribology, the coefficient of kinetic friction is determined by the Stribeck curve, as shown in Figure 3. When a lubricant is present between two solid surfaces, the coefficient of kinetic friction decreases as the viscosity of the lubricant increases, but at a certain viscosity boundary, the coefficient of kinetic friction increases again.

[0031] As shown in FIG. 3, in the Stribeck curve, in the (A) region where the viscosity of the lubricant is too low, the dynamic friction coefficient between the endoscope shaft 12 (or overtube) and the intestinal wall 14 is large and the lubricating effect is small, so the force that the intestinal wall 14 receives from the endoscope shaft 12 (or overtube) is large, resulting in greater pain and invasiveness. In the (B) region where the viscosity of the lubricant is appropriate, the dynamic friction coefficient between the endoscope shaft 12 (or overtube) and the intestinal wall 14 is small and the lubricating effect is large, so the force that the intestinal wall 14 receives from the endoscope shaft 12 (or overtube) is small, resulting in less pain and invasiveness. In the (C) region where the viscosity of the lubricant is too high, the dynamic friction coefficient between the endoscope shaft 12 (or overtube) and the intestinal wall 14 is large and the lubricating effect is small, so the force that the intestinal wall 14 receives from the endoscope shaft 12 (or overtube) is large, resulting in greater pain and invasiveness. The concentration range in which the viscosity coefficient of the thickener specified by the present inventors is the minimum is in this (B) region, and is considered to show the lowest dynamic friction coefficient.

[0032] In addition, the inventors performed a correlation analysis to determine which shear rate viscosity is most related to the dynamic friction coefficient. -1 It was found that the viscosity and the coefficient of kinetic friction at the shear rate of 100 s had the strongest correlation. -1It was found that lubricants with a viscosity in the range of 0.027 to 0.069 Pa s at the shear rate of 100 s have the physical properties to minimize the kinetic friction coefficient between the small intestinal mucosa and the overtube (see Table 1). -1 It was found that lubricants with a viscosity at shear rate in the range of 0.012 to 0.115 Pa s have the physical properties to minimize the kinetic friction coefficient between the small intestinal mucosa and the endoscope shaft (see Table 2). In order to reduce the invasiveness of small intestinal endoscopic examination, it is particularly important to reduce the kinetic friction coefficient between the small intestinal mucosa and the overtube. Furthermore, the optimal viscosity range for lubrication between the small intestinal mucosa and the overtube (0.027 to 0.069 Pa s) is included in the optimal viscosity range for lubrication between the small intestinal mucosa and the endoscope shaft (0.012 to 0.115 Pa s). Therefore, at 25°C and 100 s, -1 The report concluded that a lubricant with a viscosity at shear rate in the range of 0.027 to 0.069 Pa·s is "a lubricant with ideal physical properties for use in inserting a small intestinal endoscope" that minimizes the kinetic friction coefficient between the small intestinal mucosa and the endoscope shaft or overtube.

[0033] Thus, to minimize the kinetic friction coefficient between the small intestinal mucosa and the endoscope shaft or overtube, the lubricant should be kept at 25°C for 100 s. -1 Ideally, the viscosity at the shear rate should be in the range of 0.027 to 0.069 Pa s. In addition, the concentration and viscosity range in which the dynamic friction coefficient is not the minimum but is extremely low was defined as the acceptable viscosity range (when the dynamic friction coefficient is the minimum, the optimal viscosity range is defined as above). The acceptable viscosity range for lubrication between the small intestinal mucosa and the overtube was 0.008 to 0.302 Pa s (see Table 1), and the acceptable viscosity range for lubrication between the small intestinal mucosa and the endoscope shaft was 0.008 to 0.349 Pa s (see Table 2). The acceptable viscosity range for lubrication between the small intestinal mucosa and the overtube was included in the acceptable viscosity range for lubrication between the small intestinal mucosa and the endoscope shaft, so at 25°C and 100 s -1It was stated that lubricants with a viscosity at shear rate in the range of 0.008 to 0.302 Pa·s are "lubricants with physical properties acceptable for use as lubricants for inserting small intestinal endoscopes" that reduce the dynamic friction coefficient between the small intestinal mucosa and the endoscope shaft or overtube. In the manufacture of lubricants for inserting small intestinal endoscopes, those with physical properties in the optimal viscosity range are the first choice, but if there are barriers to lubricants with physical properties in the optimal viscosity range during the manufacturing and sales process, lubricants with physical properties in the acceptable viscosity range can be the second choice.

[0034] The lubricant for inserting a small intestine endoscope according to this embodiment contains a thickener. The thickener is a lubricant that, when mixed with a solvent such as water at an arbitrary concentration, is thickened at 25° C. for 100 s. -1 There are no particular limitations as long as the viscosity at the shear rate falls within the above range.

[0035] Examples of thickeners include carboxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose, hydroxyethylcellulose, xanthan gum, guar gum, gelatin, agar, gellan gum, carrageenan, locust bean gum, gum arabic, karaya gum, tamarind seed gum, tragacanth gum, pectin, succinoglycan, sodium alginate, sodium polyacrylate, etc., and from the viewpoint of thickeners used as components of medical lubricants, carboxymethylcellulose, xanthan gum, hydroxyethylcellulose, sodium alginate, and sodium polyacrylate are preferred. The thickener may be one of these, or two or more may be used in combination.

[0036] Among these thickeners, those with pseudoplastic fluid properties, in which the viscosity decreases under high shear forces (e.g., xanthan gum, sodium polyacrylate) have a significantly lower injection pressure from an endoscope forceps hole, etc., than those with Newtonian fluid properties (e.g., carboxymethylcellulose, sodium alginate), making them easier to inject and more suitable as lubricants for inserting a small intestine endoscope. On the other hand, existing jelly-like lubricants have too high a viscosity, making injection through an endoscope forceps hole, etc., difficult.

[0037] Examples of the solvent include water such as pure water and ultrapure water, physiological saline, phosphate buffered saline, etc. The solvent is preferably water such as pure water, because the viscosity of the thickener is easily changed by the presence of cations in the solvent and lukewarm water is injected for the purpose of washing during endoscopic examination.

[0038] The concentration of the thickener in the solvent is 25°C, 100s -1 There is no particular limitation as long as the viscosity at the shear rate is within the above range. As shown in the examples, the dynamic friction coefficient is minimum for, for example, 1.0 mass% carboxymethylcellulose (CMC), 0.5 mass% xanthan gum (XG), 0.5 mass% hydroxyethylcellulose (HEC), 0.5 mass% sodium alginate (SA), and 0.2 mass% sodium polyacrylate (SPA) in water, but the dynamic friction coefficient is low and can be used as a lubricant if the concentration in water is, for example, 0.5 to 2.0 mass% for carboxymethylcellulose (CMC), 0.1 to 1.5 mass% for xanthan gum (XG), 0.1 to 1.0 mass% for hydroxyethylcellulose (HEC), 0.05 to 1.0 mass% for sodium alginate (SA), or 0.025 to 0.3 mass% for sodium polyacrylate (SPA) (see Table 1).

[0039] The lubricant for insertion of a small intestine endoscope according to this embodiment may contain other components such as salts and buffers in addition to a thickener and a solvent such as water. Even when the lubricant for insertion of a small intestine endoscope contains components other than a thickener and a solvent, it is possible to measure the viscosity of the lubricant at 25° C. for 100 s. -1 The viscosity at the shear rate may be adjusted to fall within the above range.

[0040] The overtube is made of, for example, polyurethane or silicone, and the inner cavity of the overtube is usually coated with a hydrophilic coating, and the dynamic friction coefficient between the endoscope shaft and the overtube in the presence of water is originally very low (for example, 0.05 or less). On the other hand, the hydrophilic coating easily falls off due to the accumulation of contact between the endoscope shaft and the inner cavity of the overtube, and the friction coefficient increases over time. In fact, when a small intestine endoscopy takes a long time, the movement of the endoscope inside the overtube may become very poor. Therefore, the present inventors have also investigated how to prevent the hydrophilic coating from falling off due to contact between the endoscope shaft and the inner cavity of the overtube.

[0041] The hydrophilic coating on the inner lumen of the overtube easily falls off due to the accumulation of contact with the endoscope shaft, and the friction coefficient between the overtube and the endoscope shaft increases. -1 The viscosity at a shear rate of 0.042 to 0.180 Pa s or 100 s -1 It is desirable to apply a lubricant with a viscosity in the range of 0.174 to 0.918 Pa s at a shear rate of 1000 s (e.g., equivalent to 0.5 to 2.0 mass% sodium polyacrylate) to the inner cavity of the overtube. -1 The viscosity at a shear rate of about 0.085 Pa s or 100 s -1 A lubricant with a viscosity of about 0.385 Pa·s at this shear rate is optimal.

[0042] The lubricant used to prevent the hydrophilic coating on the inner cavity of the overtube from falling off has a higher viscosity than the lubricant used between the overtube or endoscope shaft and the small intestinal mucosa. However, after being injected through the overtube injection port, the former is mixed with intestinal fluid inside and outside the overtube (in the intestinal tract) and gradually diluted, decreasing its viscosity. Therefore, the optimal viscosity range of the lubricant used between the overtube or endoscope shaft and the small intestinal mucosa at 25°C and 100 s -1The viscosity at this shear rate approaches 0.027-0.069 Pa s (allowable viscosity range: 0.008-0.302 Pa s). In this way, it is possible for one lubricant to be used both as a lubricant between the overtube or endoscope shaft and the small intestinal mucosa, and as a lubricant to prevent the hydrophilic coating on the inner cavity of the overtube from falling off. In particular, sodium polyacrylate (SPA) has a high affinity for sodium ions (Na + ) the viscosity drops rapidly, making it an ideal lubricant for both of these applications. The allowable viscosity range for lubricating the overtube or endoscope shaft and the small intestinal mucosa is 25°C, 100s -1 The viscosity ranges from 0.008 to 0.302 Pa s at shear rates of 100 s. The allowable viscosity range for lubrication to prevent hydrophilic coatings from falling off is 25°C, 100 s. -1 The viscosity at the shear rate is in the range of 0.174 to 0.918 Pa s. Considering the above dilution, -1 By injecting a lubricant with a viscosity of 0.008 to 0.918 Pa·s at a shear rate from the overtube injection port, all the lubrication required for small intestine endoscopic examination can be provided.

[0043] The lubricant for inserting a small intestine endoscope according to the present embodiment is different from the conventional jelly-like lubricant that is applied to the endoscope shaft to reduce irritation and friction of the skin of the anus, and may be applied to the intestinal mucosa by, for example, injecting the lubricant from the endoscope forceps hole or overtube inlet during endoscope insertion and applying it to the intestinal mucosa near the leading end of the endoscope or near the tip of the overtube, or applying it to the lumen of the overtube, or supplying it from the auxiliary water supply port to the leading end of the endoscope or near the tip of the overtube and applying it to the intestinal mucosa. This reduces friction between the surface of the small intestine mucosa at the bent part of the small intestine and the endoscope shaft or overtube, and reduces the burden on the intestinal wall of the small intestine, making it possible to reduce pain and invasiveness when inserting the endoscope in small intestine endoscopy. Furthermore, it is possible to suppress the hydrophilic coating from falling off the lumen of the overtube.

[0044] In a small intestine endoscope that uses an overtube to observe the small intestine, which is located deeper than the large intestine, the intestinal wall of the small intestine as well as the large intestine is subjected to considerable force from the endoscope, and the pain and invasiveness are greater than in a large intestine endoscopy. Although a small intestine endoscopy is a difficult examination, the invasiveness of the small intestine endoscopy can be reduced by using the lubricant for inserting a small intestine endoscope according to this embodiment.

[0045] For example, it is expected that the pain during endoscope insertion and the incidence of complications during small intestine endoscopy, such as single-balloon endoscopy (SBE) using a single-balloon endoscope and double-balloon endoscopy (DBE) using a double-balloon endoscope, can be alleviated. Currently, since single-balloon overtubes and double-balloon overtubes that are commonly used have similar coefficients of friction, it is possible to lubricate either type of overtube with the lubricant for small intestine endoscope insertion according to this embodiment.

[0046] Small intestine endoscopy is associated with a high incidence of pain and complications, and is a highly invasive examination in the digestive tract, so it is often performed as an outpatient same-day examination but requires hospitalization, but the use of the lubricant for small intestine endoscope insertion according to this embodiment is expected to increase the examination completion rate and shorten the total examination time. It is also expected to lower the hurdle for performing small intestine endoscopy and expand the scope of application of small intestine endoscopy. EXAMPLES

[0047] EXAMPLES The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to the following examples.

[0048] [Relationship between the dynamic friction coefficient between the digestive tract mucosa and the endoscope shaft and the load / stress (N) applied to the intestine] A lubricant was prepared using hydroxyethyl cellulose (HEC) as a thickener and pure water as a solvent, and the relationship between the dynamic friction coefficient between the gastrointestinal mucosa and the shaft (made of resin) of an endoscope (Olympus, CF-Q260AI) and the load and strain (N) applied to the intestine was investigated. Specifically, solutions of hydroxyethyl cellulose were prepared in pure water at concentrations of 0 mass%, 0.1 mass%, 0.25 mass%, 0.5 mass%, 0.9 mass%, and 2.0 mass%, and used as lubricants. A colon specimen taken from an autopsy specimen was fixed on the weighing dish of an electronic analytical balance (HL-3000LWP, A&D, Tokyo, Japan), and the intestinal curvature was reproduced using an overtube (TOP, Tokyo, Japan). 0.5 mL of lubricant was evenly applied to the mucosa of the colon specimen, and the endoscope shaft was brought into contact with the colon mucosa, and the colonoscope was inserted 10 cm at a speed of 1 cm / s. The maximum load measured when the endoscope was inserted was taken as the load applied to the intestine (see Figure 4).

[0049] The coefficient of kinetic friction between the colon mucosa and the endoscope shaft was calculated using Tribosoft (Shinto Scientific) based on data measured using a TRIBOGEAR TYPE 38 (Shinto Scientific, Tokyo, Japan) (Fig. 5A). The colon autopsy specimen was fixed to the moving stage under a constant tension, and the endoscope shaft was attached to the measurement jig to measure the coefficient of kinetic friction between the colon mucosa and the endoscope shaft (Fig. 5B). 0.5 mL of lubricant was evenly applied to the mucosa of the colon autopsy specimen, and the endoscope shaft was brought into contact with the colon mucosa (Fig. 5C). The moving stage was set to move 50 mm over 10 strokes at a speed of 1.0 cm / s. The average value of the coefficient of kinetic friction measured during the 10 strokes of the moving table was taken as the measured value (Fig. 5D). The results are shown in Figs. 6 and 7.

[0050] The load values ​​were 1600.7 ± 122.2 mN for distilled water, 1274.0 ± 80.0 mN for 0.1% HEC, 947.3 ± 104.1 mN for 0.25% HEC, 659.9 ± 51.4 mN for 0.5% HEC, 620.7 ± 46.2 mN for 0.9% HEC, and 1143.3 ± 46.2 mN for 2.0% HEC (Figure 6). The coefficient of kinetic friction between the colonic mucosa and the endoscope shaft was 0.131 ± 0.006 for distilled water, 0.111 ± 0.016 for 0.1% HEC, 0.098 ± 0.025 for 0.25% HEC, 0.087 ± 0.022 for 0.5% HEC, 0.083 ± 0.012 for 0.9% HEC, and 0.097 ± 0.012 for 2.0% HEC (Figure 6). When a 0.5% HEC-based lubricant was used, both the coefficient of kinetic friction and the load were the lowest.

[0051] As a result of the correlation analysis, as can be seen in Figure 7, it was found that there is a strong positive correlation between the kinetic friction coefficient between the digestive mucosa and the endoscope shaft and the load / stress (N) on the intestine (correlation coefficient R = 0.965). This shows that a lower kinetic friction coefficient between the digestive mucosa and the endoscope shaft reduces the strain on the digestive tract wall.

[0052] Based on this model, we made some improvements and constructed a model that can accurately measure the friction between the endoscope shaft or overtube and the human small intestinal mucosa. Furthermore, we also constructed a model that can measure the kinetic friction coefficient between the overtube and the endoscope shaft.

[0053] <Example 1> [Measurement of lubricant viscosity and evaluation of friction between the overtube and the small intestinal mucosa] Lubricants were prepared using carboxymethylcellulose (CMC), xanthan gum (XG), hydroxyethylcellulose (HEC), sodium alginate (SA), and sodium polyacrylate (SPA) as thickeners and pure water as a solvent. Solutions were prepared with the concentration of each thickener in a given range between 0 and 4 mass%, and the viscosity (1s -1 , 10s -1 , 100s -1 , 1000s -1) was measured. Specifically, a Discovery HR-1 rheometer (TA Instruments, Surrey, UK) was used for the measurement. The temperature was controlled at 25°C using a Peltier plate, and a 60 mm cone plate was used to measure the steady flow viscosity in flow sweep mode. Next, the dynamic friction coefficient between the overtube and the small intestinal mucosa was measured using the same method as above. The results are shown in Figures 8 to 12 and Table 1.

[0054] [Table 1]

[0055] The concentration of each thickener was adjusted within a predetermined range between 0 and 4% by mass, and the concentration range in which the kinetic friction coefficient between the overtube and the small intestinal mucosa was minimized was identified. The kinetic friction coefficients of 1.0% by mass CMC, 0.5% by mass XG, 0.5% by mass HEC, 0.5% by mass SA, and 0.2% by mass SPA were the smallest at around 0.019 (0.015 to 0.025). In addition, the kinetic friction coefficients of CMC in the concentration range of 0.5 to 2.0% by mass, XG in the concentration range of 0.1 to 1.5% by mass, HEC in the concentration range of 0.1 to 1.0% by mass, SA in the concentration range of 0.05 to 1.0% by mass, and SPA in the concentration range of 0.025 to 0.3% by mass were not the smallest, but showed extremely low values. This concentration range was defined as the acceptable range concentration.

[0056] As mentioned above, from the viewpoint of tribology, the coefficient of kinetic friction is determined by the Stribeck curve. As the viscosity of the lubricant increases, the coefficient of kinetic friction decreases, but at a certain viscosity boundary, the coefficient of kinetic friction increases again. The above-mentioned thickener concentration is the viscosity at this boundary, and is thought to show the minimum coefficient of kinetic friction. Also, at what shear rate (1 s -1 , 10s -1 , 100s -1 , 1000s -1 A correlation analysis was performed to determine whether the viscosity of the liquid is most closely related to the dynamic friction coefficient between the overtube and the small intestinal mucosa. The results are shown in Figure 13.

[0057] As a result, the coefficient of kinetic friction between the overtube and the small intestinal mucosa was 100s -1It was found that the shear rate of the solution had the strongest correlation with the viscosity at 25°C and 100s (correlation coefficient R = 0.88). -1 A lubricant with a viscosity of 0.027 to 0.069 Pa·s at a shear rate of 100 s is the ideal lubricant with the physical properties to minimize the kinetic friction coefficient between the overtube and the small intestinal mucosa. -1 Lubricants with a viscosity in the range of 0.008 to 0.302 Pa·s at this shear rate are the second choice of lubricants because they have a very low coefficient of kinetic friction (see Table 1).

[0058] <Example 2> [Evaluation of friction between the endoscope shaft and the small intestinal mucosa] Solutions were prepared in which the concentration of each thickener in pure water was within a prescribed range between 0 and 4% by mass, and the dynamic friction coefficient between the endoscope shaft and the small intestinal mucosa was measured in the same manner as above. The results are shown in Figures 14 to 18 and Table 2.

[0059] [Table 2]

[0060] The concentration of each thickener was adjusted within a predetermined range between 0 and 4% by mass, and the concentration range in which the kinetic friction coefficient between the endoscope shaft and the small intestinal mucosa was determined to be the smallest was found to have the smallest kinetic friction coefficients of around 0.054 (0.041 to 0.095) for 1.0% by mass CMC, 1.0% by mass XG, 1.0% by mass HEC, 0.1% by mass SA, and 0.1% by mass SPA. In addition, the kinetic friction coefficients of CMC in the concentration range of 0.5 to 2.5% by mass, XG in the concentration range of 0.5 to 1.5% by mass, HEC in the concentration range of 0.5 to 2.0% by mass, SA in the concentration range of 0.05 to 1.0% by mass, and SPA in the concentration range of 0.075 to 0.3% by mass were not the smallest, but showed extremely low values. This concentration range was defined as the acceptable concentration range.

[0061] As mentioned above, from the viewpoint of tribology, the coefficient of kinetic friction is determined by the Stribeck curve. As the viscosity of the lubricant increases, the coefficient of kinetic friction decreases, but at a certain viscosity boundary, the coefficient of kinetic friction increases again. The above-mentioned thickener concentration is the viscosity at this boundary, and is thought to show the minimum coefficient of kinetic friction. Also, at what shear rate (1 s -1 , 10s -1 , 100s -1 , 1000s -1 A correlation analysis was performed to determine whether the viscosity of the endoscope is most closely related to the coefficient of kinetic friction between the endoscope shaft and the small intestinal mucosa. The results are shown in Figure 19.

[0062] As a result, the coefficient of dynamic friction between the endoscope shaft and the small intestinal mucosa was 100s -1 It was found that the shear rate of the solution had the strongest correlation with the viscosity at 25°C and 100s (correlation coefficient R = 0.74). -1 A lubricant with a viscosity of 0.012 to 0.115 Pa·s at a shear rate of 100 s is the ideal lubricant with the physical properties to minimize the kinetic friction coefficient between the endoscope shaft and the small intestine mucosa. -1 Lubricants with a viscosity in the range of 0.008 to 0.349 Pa·s at this shear rate are the second choice of lubricants because they have a very low coefficient of kinetic friction (see Table 2).

[0063] <Example 3> [Friction evaluation of the endoscope shaft and overtube] We investigated how to prevent the hydrophilic coating from falling off due to contact between the endoscope shaft and the inner cavity of the overtube. Specifically, a lubricant containing sodium polyacrylate (SPA) in pure water as a thickener was applied to the inner cavity of the overtube for a single balloon endoscope or a double balloon endoscope, which was coated with a hydrophilic coating. As shown in Figure 20, the endoscope shaft 12 inserted into the inner cavity of the overtube 18 was repeatedly moved, and the contact between the inner cavity of the endoscope shaft 12 and the overtube 18 due to the repeated movement was continued, and the change in the dynamic friction coefficient of the endoscope shaft 12 and the overtube 18 was measured over time. Note that the time elapsed corresponds to the number of repetitions. Solutions were prepared with concentrations of sodium polyacrylate (SPA) of 0, 0.1, 0.5, 1.0, and 2.0% by mass, and the dynamic friction coefficient between the endoscope shaft and the overtube was measured in the same manner as above. The results are shown in Figure 21 and Table 3.

[0064] [Table 3]

[0065] As a result, under the condition of 0.5 to 1.0 mass% SPA, in other words, the viscosity (25°C, 1000s -1 ) was 0.042 to 0.085 Pa s, there was almost no increase in the dynamic friction coefficient, and the hydrophilic coating was maintained for a long period of time. Under other conditions (including pure water conditions (0 mass% SPA)), the dynamic friction coefficient increased with increasing time (number of repetitions), and the hydrophilic coating fell off. Figure 22 is a photograph showing a part of the inner surface of the overtube with a hydrophilic coating (top), and a part where the hydrophilic coating fell off due to contact between the endoscope shaft and the inner lumen of the overtube (bottom).

[0066] Therefore, at 25°C, 1000s -1 The viscosity at shear rates is in the range of 0.042 to 0.085 Pa s (at 25°C for 100 s -1It was found that applying a lubricant (e.g., 0.5 to 1.0 mass% SPA) with a viscosity of 0.174 to 0.385 Pa s at shear rate of 100 s to the inside of the overtube makes the hydrophilic coating less likely to peel off. -1 The lubricant with a viscosity of 0.918 Pa·s at a shear rate of 100 s was also found to be effective, so it is considered that it can be used under certain circumstances. -1 Lubricants with a viscosity at this shear rate in the range of 0.174 to 0.918 Pa·s (for example, 0.5 to 2.0 mass % SPA) can be used (see Table 3).

[0067] Next, we investigated the application of a lubricant to reduce the dynamic friction coefficient when the hydrophilic coating falls off from the inner surface of the overtube.

[0068] Lubricants were prepared by adjusting the concentration of sodium polyacrylate (SPA) as a thickener in pure water to 0.0, 0.5, 1.0, 2.0, and 4.0% by mass, and these were applied to the inner surface of the overtube from which the hydrophilic coating had fallen off, and the dynamic friction coefficient between the endoscope shaft and the overtube was measured using the same method as above. The results are shown in Figure 23 and Table 4.

[0069] [Table 4] When the concentration range in which the dynamic friction coefficient between the endoscope shaft and the overtube was minimized was identified, the dynamic friction coefficient of 4.0 mass% SPA was the smallest at 0.26. In addition, the dynamic friction coefficient of SPA in the concentration range of 1.0 to 4.0 mass% was not the smallest, but was extremely low. This concentration range is defined as the acceptable concentration range.

[0070] Also, what shear rate (1s -1 , 10s -1 , 100s -1 , 1000s -1 A correlation analysis was performed to determine whether the viscosity of the endoscope is most closely related to the dynamic friction coefficient between the endoscope shaft and the overtube. The results are shown in Figure 24.

[0071] As a result, the coefficient of dynamic friction between the endoscope shaft and the overtube was 1000s -1 It was found that the shear rate had the strongest correlation with the viscosity (correlation coefficient R = 0.97).

[0072] If the hydrophilic coating falls off, the dynamic friction coefficient between the endoscope shaft and the overtube becomes extremely high. For example, as can be seen from the results for pure water conditions (0 mass% SPA) in Figure 21, the dynamic friction coefficient approaches 1.0, and the overtube from which the hydrophilic coating has fallen off will hinder the passage of the endoscope shaft. If the hydrophilic coating falls off, the dynamic friction coefficient can be reduced by applying a high-viscosity lubricant to the inside of the overtube. For example, at 25°C and 1000 s -1 The viscosity at a shear rate of 0.365 Pa s (25°C, 100 s -1 By applying a lubricant with a viscosity of 2.35 Pa s at a shear rate of 1000 s (e.g., a lubricant containing 4.0 mass% SPA), the dynamic friction coefficient could be reduced to 0.26. -1 The viscosity at shear rates is in the range of 0.085 to 0.356 Pa s (25°C, 100 s -1 By applying a lubricant with a viscosity in the range of 0.385 to 2.35 Pa·s at the shear rate (e.g., a lubricant containing 1.0 to 4.0 mass% SPA), the dynamic friction coefficient showed a low value.

[0073] A solution containing 0.5% by mass of sodium polyacrylate (SPA) in pure water, a solution containing 1.0% by mass of sodium polyacrylate (SPA) in pure water, a solution containing 0.5% by mass of sodium polyacrylate (SPA) and 0.9% by mass of sodium ions (Na + ), a solution containing 1.0% by mass of sodium polyacrylate (SPA) and 0.9% by mass of sodium ions (Na + ) for a solution containing -1 , 1s -1 , 10s -1 , 100s -1 , 1000s -1The viscosity of the endoscope was measured. The coefficient of dynamic friction between the overtube (OC) and the small intestinal mucosa (M), and between the endoscope shaft (S) and the small intestinal mucosa (M) were also measured. The results are shown in Table 5.

[0074] [Table 5]

[0075] Sodium polyacrylate (SPA) is a compound that contains sodium ions (Na + ) and the viscosity decreases, and the friction coefficient also decreases accordingly. For example, 0.5% by mass SPA reacts with sodium ions and the viscosity decreases to that of 0.35% by mass SPA. When it is further diluted to about 20% by mass SPA, the viscosity becomes equivalent to that of 0.3% by mass SPA. At that time, the kinetic friction coefficient between the overtube and the small intestinal mucosa becomes 0.015, which is almost the minimum friction coefficient.

[0076] As described above, the lubricants of the Examples made it possible to alleviate pain and reduce invasiveness during insertion of an endoscope into the small intestine. [Explanation of symbols]

[0077] 10: intestinal bend, 12: endoscope shaft, 14: intestinal wall, 16: lubricant, 18: overtube.

Claims

1. 25°C, 100s －１ The lubricant for inserting a small intestine endoscope has a viscosity at a shear rate in the range of 0.008 to 0.918 Pa·s.

2. The lubricant for inserting a small intestine endoscope according to claim 1, A lubricant for use in inserting a small intestine endoscope, characterized in that the viscosity at the shear rate is in the range of 0.027 to 0.069 Pa·s.

3. The lubricant for inserting a small intestine endoscope according to claim 1 or 2, A lubricant for use in inserting a small intestine endoscope, comprising at least one of carboxymethyl cellulose, xanthan gum, hydroxyethyl cellulose, sodium alginate, and sodium polyacrylate.

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