Submucosal injection material for endoscopy

Abstract

A submucosal injection material for endoscopy that comprises water and a polysaccharide represented by general formula (1). In general formula (1): R1, R2 and R3 independently represent a hydrogen atom, etc.; n represents an integer of 100-100,000; k represents 0 or 1; m represents an integer of 1-10; and j represents an integer of 6-26. The polysaccharide represented by general formula (1) has at least one -CH2CH(OH)CH2OCjH2j+1.

Description

[Technical Field]

[0001] The present disclosure relates to an endoscopic submucosal injection material. [Background technology]

[0002] Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are known as treatments for gastrointestinal polyps, early gastric cancer, and early colorectal cancer. In EMR or ESD, an endoscopic submucosal injection material is injected into the submucosal layer of the lesion to elevate the mucosa below the lesion, in order to facilitate resection.

[0003] For example, Japanese Patent Application Laid-Open No. 2001-192336 discloses a submucosal injection material for endoscopy containing sodium hyaluronate. Furthermore, Japanese Patent Application Laid-Open No. 2014-188054 discloses a submucosal injection material for endoscopy that contains sodium alginate. Furthermore, Japanese Patent Publication No. 2017-506208 discloses a submucosal injection material for endoscopy containing carboxymethyl cellulose, hydroxypropyl ethyl cellulose, xanthan gum, etc. Furthermore, International Publication No. 2013 / 077357 discloses a submucosal injection material for endoscopy that contains xanthan gum. Summary of the Invention [Problem to be solved by the invention]

[0004] Submucosal injection materials for endoscopy are required to have excellent protuberance and protuberance maintenance properties, but the submucosal injection materials for endoscopy disclosed in JP 2001-192336 A and JP 2014-188054 A did not have sufficient protuberance and protuberance maintenance properties, and there was room for improvement.

[0005] Furthermore, the endoscopic submucosal injection material containing carboxymethyl cellulose or hydroxypropyl ethyl cellulose disclosed in JP 2017-506208 A does not have sufficient protuberance and protuberance maintenance, and requires high pressure for injection into the submucosal layer, leaving room for improvement in ease of injection.

[0006] Polysaccharides such as carboxymethylcellulose and xanthan gum after synthesis may contain bacterial impurities (endotoxins, etc.), and therefore must be purified by strong alkaline decomposition, filter filtration, etc. before being incorporated into an endoscopic submucosal injection material. Furthermore, purification by filter filtration increases production costs due to the need to prepare the equipment, etc., so purification by strong alkaline decomposition is preferred. The endoscopic submucosal injection materials disclosed in JP 2017-506208 A and WO 2013 / 077357 A contain xanthan gum, but xanthan gum is denatured by strong alkaline decomposition treatment, making it impossible to obtain a submucosal injection material for endoscopy. Furthermore, since an aqueous xanthan gum solution has a high viscosity, when the solution is subjected to a filter filtration treatment, the solution must be diluted beforehand, and after dilution, the concentration of the xanthan gum must be adjusted. Therefore, the submucosal injection materials for endoscopy disclosed in JP2017-506208A and WO2013 / 077357A have room for improvement in terms of manufacturability.

[0007] The present disclosure has been made in consideration of the above problems, and the problem it aims to solve is to provide a submucosal injection material for endoscopy that is excellent in terms of protuberance, protuberance maintenance, ease of injection, and manufacturability. [Means for solving the problem]

[0008] The specific means for achieving the objectives are as follows: <1> A submucosal injection material for endoscopy, comprising water and a polysaccharide represented by general formula (1).

[0009] [ka]

[0010] In general formula (1), R 1 , R 2 and R 3 are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or -[CHCH 2-k (CH3) k O] m H, or -CH2CH(OH)CH2OC j H 2j+1 indicates, n represents an integer from 100 to 100,000; k represents 0 or 1; m represents an integer from 1 to 10; j represents an integer from 6 to 26; The polysaccharide represented by the general formula (1) is -CH2CH(OH)CH2OC j H 2j+1 has at least one <2> The ratio of viscosity at a temperature of 25°C and a frequency of 1 Hz to viscosity at a temperature of 25°C and a frequency of 100 Hz is 10 or more. <1> The submucosal injection material for endoscopy according to claim 1. <3> The viscosity at a temperature of 25°C and a frequency of 100 Hz is 150 mPa·s or less. <1> or <2> The submucosal injection material for endoscopy according to claim 1. <4> The viscosity at a temperature of 25°C and a frequency of 1 Hz is 2000 mPa·s or more. <1> ~ <3> 10. The submucosal injection material for endoscopy according to claim 1, wherein the submucosal injection material is a <5> In the general formula (1), j is an integer of 10 to 20. <1> ~ <4> 10. The submucosal injection material for endoscopy according to claim 1, wherein the submucosal injection material is a <6> The polysaccharide comprises stearylated hydroxypropyl methylcellulose. <1> ~ <5> 10. The submucosal injection material for endoscopy according to claim 1, wherein the submucosal injection material is a <7> -CH2CH(OH)CH2OC relative to the mass of the polysaccharide j H 2j+1The content of the above is 0.2% by mass to 1.0% by mass. <1> ~ <6> 10. The submucosal injection material for endoscopy according to claim 1, wherein the submucosal injection material is a <8> The content of the polysaccharide relative to the mass of the endoscopic submucosal injection material is 0.1% by mass to 0.5% by mass. <1> ~ <7> 10. The submucosal injection material for endoscopy according to claim 1, wherein the submucosal injection material is a <9> The above organic compound has a molecular weight of 400 or less and contains two or more hydroxyl groups. <1> ~ <8> 10. The submucosal injection material for endoscopy according to claim 1, wherein the submucosal injection material is a <10> The content of the organic compound relative to the mass of the endoscopic submucosal injection material is 0.1% by mass or more. <9> The submucosal injection material for endoscopy according to claim 1. [Effects of the Invention]

[0011] According to the present disclosure, it is possible to provide a submucosal injection material for endoscopy that is excellent in terms of protuberance, protuberance maintenance, ease of injection, and manufacturability. DETAILED DESCRIPTION OF THE INVENTION

[0012] In the present disclosure, numerical ranges indicated using "to" include the numerical values ​​before and after "to" as the minimum and maximum values, respectively. In the numerical ranges described in stages in the present disclosure, the upper or lower limit value described in one numerical range may be replaced with the upper or lower limit value of another numerical range described in stages. Furthermore, in the numerical ranges described in the present disclosure, the upper or lower limit value of the numerical range may be replaced with the value shown in the synthesis examples.

[0013] In the present disclosure, the viscosity of the submucosal injection material for endoscopy is measured by setting the temperature of the submucosal injection material for endoscopy to 25°C and using a rheometer. As the rheometer, a rheometer (manufactured by Anton Paar, automatic rheometer MCR102) equipped with a cone-plate type jig (parallel plate, 10 mmΦ) or a device of the same level can be used.

[0014] In the present disclosure, the weight average molecular weight (Mw) is a value measured using the following GPC measurement device under the following measurement conditions and converted using a calibration curve of standard polystyrene. The calibration curve was created using a set of five standard polystyrene samples ("PStQuick MP-H" and "PStQuick B", manufactured by Tosoh Corporation). (GPC measurement device) GPC equipment: High-speed GPC equipment "HCL-8320GPC", detector is differential refractometer or UV, manufactured by Tosoh Corporation Columns: TSKgel SuperHZM-H, TSKgel SuperHZ4000, and TSKgel SuperHZ200 (all manufactured by Tosoh Corporation) were connected in series in this order. (Measurement conditions) Solvent: N-methylpyrrolidone (NMP) Column temperature: 40℃

[0015] In the present disclosure, the content of alkyl groups having 1 to 4 carbon atoms relative to the mass of the polysaccharide represented by general formula (1), -[CHCH 2-k (CH3) k O] m H content and -CH2CH(OH)CH2OC j H 2j+1 The content is measured by the method according to the hydroxypropyl methylcellulose 2208 section of the Japanese Pharmacopoeia, 13th Edition.

[0016] <Submucosal injection material for endoscopy> The submucosal injection material for endoscopy of the present disclosure contains a polysaccharide represented by general formula (1) and water.

[0017] [ka]

[0018] In general formula (1), R 1 , R 2 and R 3are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or -[CHCH 2-k (CH3) k O] m H, or -CH2CH(OH)CH2OC j H 2j+1 indicates, n represents an integer from 100 to 100,000; k represents 0 or 1; m represents an integer from 1 to 10; j represents an integer from 6 to 26; The polysaccharide represented by the general formula (1) is -CH2CH(OH)CH2OC j H 2j+1 has at least one

[0019] The submucosal injection material for endoscopy of the present disclosure has excellent protuberance, protuberance maintenance, ease of injection, and manufacturability.

[0020] The reason for the above effect is presumed to be as follows, but is not limited to this. The polysaccharide represented by general formula (1) contained in the submucosal injection material for endoscopy disclosed herein is -CH2CH(OH)CH2OC j H 2j+1 (hereinafter also referred to as a specific group). It is presumed that when no force such as pressure is applied or only a small force is applied, the polysaccharide aggregates due to the hydrophobic interaction of the specific group, thereby improving the protuberance and the ability to maintain the protuberance. Furthermore, it is presumed that the pressure applied to the endoscopic submucosal injection material during injection will eliminate the hydrophobic interaction and reduce the viscosity of the endoscopic submucosal injection material, thereby improving ease of injection. Furthermore, the polysaccharide represented by general formula (1) has a cellulose ether skeleton and is presumed to have excellent suitability for strong alkaline decomposition treatment.

[0021] The viscosity of the endoscopic submucosal injection material at a temperature of 25°C and a frequency of 100 Hz is preferably 200 mPa s or less, more preferably 150 mPa s or less, and even more preferably 100 mPa s or less. A viscosity of 200 mPa s or less can further improve ease of injection. The lower limit of the viscosity is not particularly limited, but can be, for example, 10 mPa·s or more.

[0022] The viscosity of the endoscopic submucosal injection material at a temperature of 25°C and a frequency of 1 Hz is preferably 1500 mPa·s or more, more preferably 2000 mPa·s or more, and even more preferably 2500 mPa·s or more. A viscosity of 1500 mPa·s or more can further improve the protuberance and the ability to maintain the protuberance. The upper limit of the viscosity is not particularly limited, but can be set to, for example, 100,000 mPa·s or less.

[0023] From the viewpoints of protuberance, protuberance maintenance, and ease of injection, the ratio of the viscosity of the endoscopic submucosal injection material at a temperature of 25°C and a frequency of 1 Hz to the viscosity of the endoscopic submucosal injection material at a temperature of 25°C and a frequency of 100 Hz is preferably 10 or more, more preferably 20 or more, even more preferably 30 or more, and particularly preferably 35 or more.

[0024] From the viewpoint of safety, the osmotic pressure ratio of the submucosal injection material for endoscopy to physiological saline is preferably 0.7 to 1.5. In the present disclosure, osmotic pressure is measured using an osmometer (OSMOMAT300(D) manufactured by Gonotec) or a similar device in accordance with 2.47 Osmolality Measurement Method (Osmolality Measurement Method) of the 17th Revised Japanese Pharmacopoeia (Ministry of Health, Labour and Welfare Notification No. 64, March 7, 2016). The physiological saline used was Otsuka saline injection (manufactured by Otsuka Pharmaceutical Co., Ltd., osmolality 288 mOsmol / kg), and the measured osmolality was divided by the osmolality value of Otsuka saline injection to determine the osmolality ratio.

[0025] From the viewpoint of safety, the endotoxin content of the submucosal injection material for endoscopy is preferably 0.1 EU / mL or less. In the present disclosure, the amount of endotoxin is measured according to the gelation method of the 17th revision of the Japanese Pharmacopoeia (Ministry of Health, Labour and Welfare Notification No. 64, March 7, 2016). Limulus Color KY Test Wako is used as the endotoxin measurement reagent, and the Japanese Pharmacopoeia endotoxin standard is used as the endotoxin standard.

[0026] (Polysaccharides represented by general formula (1)) In general formula (1), R 1 , R 2 and R 3 are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or -[CHCH 2-k (CH3) k O] m H, or -CH2CH(OH)CH2OC j H 2j+1 Shows. Also, when n is 2 or more, 2 or more R 1 etc. may be the same or different.

[0027] The alkyl group having 1 to 4 carbon atoms may be linear or branched. Examples of the alkyl group having 1 to 4 carbon atoms include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, and a t-butyl group.

[0028] The content of alkyl groups having 1 to 4 carbon atoms relative to the mass of the polysaccharide represented by general formula (1) is preferably 10% by mass to 50% by mass.

[0029] -[CH2CH 2-k (CH3) k O] m In H, k represents 0 or 1. Furthermore, m represents an integer of 1 to 10, preferably an integer of 1 to 5, and more preferably 1.

[0030] -[CH2CH2-k (CH3) k O] m The H content is preferably 3% to 20% by mass.

[0031] -CH2CH(OH)CH2OC j H 2j+1 In the formula, j represents an integer of 6 to 26, and from the viewpoints of the protuberance, protuberance maintenance, and ease of injection, it preferably represents an integer of 10 to 20, and more preferably represents an integer of 15 to 18.

[0032] From the viewpoint of swelling, swelling retention, and ease of injection, the ratio of -CH2CH(OH)CH2OC to the mass of the polysaccharide represented by general formula (1) j H 2j+1 The content is preferably 0.1% by mass to 10% by mass, more preferably 0.2% by mass to 1.0% by mass, and even more preferably 0.3% by mass to 0.6% by mass.

[0033] In general formula (1), n ​​represents an integer of 100 to 100,000, preferably an integer of 100 to 10,000, and more preferably an integer of 2,000 to 4,000.

[0034] The Mw of the polysaccharide represented by general formula (1) is preferably 10,000 to 10,000,000, more preferably 50,000 to 5,000,000, and even more preferably 100,000 to 1,000,000.

[0035] Examples of polysaccharides satisfying the general formula (1) include palmitoylated hydroxypropyl methylcellulose, margaryl hydroxypropyl methylcellulose, and stearylated hydroxypropyl methylcellulose. From the viewpoints of protuberance, protuberance maintenance, and ease of injection, the polysaccharide satisfying the general formula (1) preferably includes stearylated hydroxypropylmethylcellulose.

[0036] From the viewpoints of protuberance, protuberance maintenance, and ease of injection, the content of the polysaccharide represented by general formula (1) relative to the mass of the endoscopic submucosal injection material is preferably 0.1% by mass to 0.5% by mass, and more preferably 0.25% by mass to 0.35% by mass. The endoscopic submucosal injection material may contain two or more types of polysaccharides represented by general formula (1). The two or more types of polysaccharides represented by general formula (1) may be structural isomers.

[0037] From the viewpoints of protuberance, protuberance maintenance, and ease of injection, the content of stearylated hydroxypropyl methylcellulose relative to the total mass of polysaccharides satisfying general formula (1) contained in the endoscopic submucosal injection material is preferably 50% by mass to 100% by mass, and more preferably 70% by mass to 100% by mass. The polysaccharide satisfying the general formula (1) may contain two or more types of stearylated hydroxypropylmethylcellulose.

[0038] The polysaccharide represented by the general formula (1) may be one produced by a conventionally known method or may be a commercially available product. Commercially available products include Saint-Gelose (registered trademark) 90L and Saint-Gelose (registered trademark) 60L manufactured by Daido Chemical Industry Co., Ltd. Sangelose (registered trademark) 90L and Sangelose (registered trademark) 60L are products that have been subjected to a strong alkali decomposition treatment using a high-concentration aqueous sodium hydroxide solution (approximately 15% to 40% by mass) during the synthesis of stearylated hydroxypropyl methylcellulose. Specifically, the strong alkali decomposition treatment is carried out by impregnating cellulose with a high-concentration aqueous sodium hydroxide solution. The cellulose after the strong alkali decomposition treatment (alkali cellulose) is then used to synthesize stearylated hydroxypropyl methylcellulose.

[0039] (water) Examples of water include ion-exchanged water, pure water, and purified water. Among these, pure water or purified water is preferred in view of its applicability to endoscopic submucosal injection materials. Purified water in which sodium chloride, an organic compound, or the like described below is dispersed or dissolved may also be used.

[0040] The water content relative to the mass of the endoscopic submucosal injection material is not particularly limited, but can be, for example, 80% by mass to 99.9% by mass.

[0041] (An organic compound with a molecular weight of 400 or less and two or more hydroxyl groups) The submucosal injection material for endoscopy of the present disclosure may contain an organic compound having a molecular weight of 400 or less and having two or more hydroxyl groups. When the submucosal injection material for endoscopy contains the organic compound, the osmotic pressure of the submucosal injection material for endoscopy can be adjusted. The molecular weight of the organic compound is preferably 200 or less, and more preferably 100 or less. The lower limit of the molecular weight of the organic compound is not particularly limited, but can be, for example, 50 or more. In the present disclosure, the molecular weight of an organic compound having two or more hydroxyl groups and a molecular weight of 400 or less is determined from the chemical structure of the compound when the organic compound is a monomer, and is measured using a GPC measurement device under measurement conditions similar to those for measuring Mw when the organic compound is a polymer such as an oligomer or polymer.

[0042] Examples of the organic compound include glycol compounds, sugar alcohol compounds, monosaccharide compounds, and disaccharide compounds, and the organic compound may contain two or more of these compounds. Examples of glycol compounds include propylene glycol, triethylene glycol, and polyethylene glycol. Examples of sugar alcohol compounds include erythritol, glycerol, sorbitol, and xylitol. Examples of monosaccharide compounds include glucose, mannose, galactose, and fructose. Examples of disaccharide compounds include sucrose, lactose, lactulose, maltose, and trehalose.

[0043] The content of the organic compound relative to the mass of the endoscopic submucosal injection material is preferably 0.1% by mass or more, and more preferably 0.2% by mass or more. By setting the content of the organic compound within the above range, the osmotic pressure ratio of the endoscopic submucosal injection material to physiological saline can be set to a numerical value. The upper limit of the content of the organic compound is not particularly limited, but can be, for example, 5% by mass or less.

[0044] (others) The submucosal injection material for endoscopes of the present disclosure may contain sodium chloride. By containing sodium chloride in the submucosal injection material for endoscopes, the osmotic pressure of the submucosal injection material for endoscopes can be adjusted.

[0045] The content of the sodium chloride relative to the mass of the submucosal injection material for endoscopy is preferably in the range of 0.1% by mass to 5% by mass, and more preferably in the range of 0.5% by mass to 1% by mass. By setting the content of sodium chloride within the above range, the osmotic pressure ratio of the endoscopic submucosal injection material to physiological saline can be set to a favorable value.

[0046] The endoscopic submucosal injection material may contain polysaccharides other than the polysaccharide represented by general formula (1), such as sodium hyaluronate, xanthan gum, sodium carboxymethylcellulose, locust bean gum, dextran, dextrin, sodium alginate, hydroxyalkyl cellulose (such as hydroxypropyl ethyl cellulose), sodium carboxymethyl dextran, sodium poly(meth)acrylate, and polyvinyl alcohol. The submucosal injection material for endoscopy may contain a protein compound, such as gelatin or casein.

[0047] The endoscopic submucosal injection material may also contain a coloring agent, a contrast agent, a filler, a cancer therapeutic agent, a hormone agent, an anti-inflammatory agent, an antibiotic, an analgesic, an antibacterial agent, a pH adjuster, or the like. [Example]

[0048] The above embodiment will be specifically described below using examples, but the above embodiment is not limited to these examples.

[0049] Example 1 Polysaccharide A satisfying the general formula (1) (manufactured by Daido Chemical Industry Co., Ltd., Sangelose (registered trademark) 90L, weight average molecular weight 700,000 to 900,000, -CHCH(OH)CHOC j H 2j+1 A 0.9% sodium chloride aqueous solution (Hayashi Pure Chemical Industries, Ltd., 0.9 W / V% sodium chloride solution) was added to a polysaccharide A content of 0.3 mass% to 0.6 mass%, to prepare a submucosal injection material for endoscopy with a polysaccharide A content of 0.3 mass%. Sangelose (registered trademark) 90L contains stearylated hydroxypropyl methylcellulose, and impurities such as endotoxin have been removed during its synthesis by a strong alkaline decomposition treatment using a highly concentrated aqueous sodium hydroxide solution. The endotoxin content of the endoscopic submucosal injection material was measured according to the gelation method of the 17th revision of the Japanese Pharmacopoeia (Ministry of Health, Labour and Welfare Notification No. 64, March 7, 2016), and was found to be 0.0005 EU / mL or less (below the detection limit). The endotoxin measurement reagent used was Limulus Color KY Test Wako, and the endotoxin standard used was the Japanese Pharmacopoeia endotoxin standard.

[0050] (Examples 2 to 4) Submucosal injection materials for endoscopy were prepared in the same manner as in Example 1, except that the content of polysaccharide A was changed to the value shown in Table 1.

[0051] Example 5 Polysaccharide A was replaced with polysaccharide B (manufactured by Daido Chemical Industry Co., Ltd., Sangelose (registered trademark) 60L, weight average molecular weight 300,000 to 500,000, -CHCH(OH)CHOC) satisfying the general formula (1). j H 2j+1 A submucosal injection material for endoscopy was prepared in the same manner as in Example 1, except that the content of was changed to 0.3% by mass to 0.6% by mass. Sangelose (registered trademark) 60L contains stearylated hydroxypropyl methylcellulose, and impurities such as endotoxin have been removed during its synthesis by a strong alkaline decomposition treatment using a highly concentrated aqueous sodium hydroxide solution.

[0052] Example 6 A submucosal injection material for endoscopy was prepared in the same manner as in Example 1, except that glycerol (an organic compound having a molecular weight of 400 or less and two or more hydroxyl groups) was further added to a content of 2.6% by mass.

[0053] Example 7 A submucosal injection material for endoscopy was prepared in the same manner as in Example 1, except that the content of polysaccharide A was changed to the value shown in Table 1 and sodium carboxymethylcellulose (a polysaccharide other than the polysaccharide represented by general formula (1), manufactured by Sigma-Aldrich, weight-average molecular weight 250,000) was further added to a content of 0.25 mass%.

[0054] Example 8 Polysaccharide A and polysaccharide B were mixed with a 0.9% aqueous sodium chloride solution (Hayashi Pure Chemical Industries, Ltd., 0.9 W / V% sodium chloride solution) to prepare a submucosal injection material for endoscopy containing 0.15% by mass of polysaccharide A and 0.15% by mass of polysaccharide B.

[0055] (Comparative Example 1) A 0.9% aqueous sodium chloride solution (Hayashi Pure Chemical Industries, Ltd., 0.9 W / V% sodium chloride solution) was added to sodium hyaluronate (Fujifilm Wako Pure Chemical Industries, Ltd., sodium hyaluronate, weight-average molecular weight 1,000,000) to prepare a submucosal injection material for endoscopy with a sodium hyaluronate content of 0.4% by mass.

[0056] (Comparative Example 2) Submucosal injection materials for endoscopy were prepared in the same manner as in Comparative Example 1, except that the content of sodium hyaluronate was changed to the value shown in Table 1.

[0057] (Comparative Example 3) A 0.9% aqueous sodium chloride solution (Hayashi Pure Chemical Industries, Ltd., 0.9 W / V% sodium chloride solution) was added to sodium carboxymethylcellulose (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., sodium carboxymethylcellulose) to prepare a submucosal injection material for endoscopy with a carboxymethylcellulose sodium content of 0.5% by mass.

[0058] Comparative Example 4 Hydroxypropyl methylcellulose (Sigma-Aldrich, hydroxypropyl cellulose 2.0-2.9, weight-average molecular weight 120,000) was mixed with a 0.9% aqueous sodium chloride solution (Hayashi Pure Chemical Industries, Ltd., 0.9 W / V% sodium chloride solution) to prepare a submucosal injection material for endoscopy with a hydroxypropyl methylcellulose content of 3.0% by mass.

[0059] (Comparative Example 5) An aqueous solution containing 0.6% by mass of unpurified xanthan gum (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was prepared. The amount of endotoxin was measured in the same manner as in Example 1 and was found to be 420 EU / mL. When an attempt was made to filter the above aqueous solution using an endotoxin removal filter (Charged Durapore, pore size 0.22 μm, manufactured by Merck), the viscosity of the aqueous solution was too high to pass through the filter, and the solution could not be used to prepare a submucosal injection material for endoscopy. Furthermore, when the unpurified xanthan gum was subjected to strong alkaline decomposition treatment with a highly concentrated aqueous solution of sodium hydroxide, denaturation of the xanthan gum was confirmed, and therefore it was not used in the preparation of a submucosal injection material for endoscopy. Therefore, the following measurements and evaluations were not carried out.

[0060] <Viscosity measurement> The viscosity (hereinafter referred to as viscosity A) of the endoscopic submucosal injection materials prepared in the Examples and Comparative Examples was measured using a rheometer (Anton Paar automatic rheometer MCR102) equipped with a cone-plate type jig (parallel plate, 10 mmΦ) at a frequency of 100 Hz and a temperature of 25°C. Furthermore, the frequency was changed to 1 Hz, and the viscosity (hereinafter referred to as viscosity B) of the submucosal injection materials for endoscopy prepared in the Examples and Comparative Examples was measured at a temperature of 25°C. Furthermore, the ratio of viscosity B to viscosity A (viscosity B / viscosity A) was determined. These results are summarized in Table 1.

[0061] <Evaluation of prominence> The upper part of the excised pig stomach (the upper part when the entire length was divided into three equal parts) was cut into 5 cm squares to prepare test specimens. 2 mL of each of the endoscopic submucosal injection materials prepared in the Examples and Comparative Examples was injected into the submucosal layer of the test piece using an endoscopic puncture needle (Supergrip, manufactured by Top Corporation, needle diameter 23G). The height of the mucosal layer rise immediately after injection was measured and evaluated based on the following evaluation criteria. The evaluation results are summarized in Table 1. The height of the protrusion was measured using a laser displacement sensor with a built-in camera, IX-150, manufactured by Keyence Corporation, and the maximum height of the protrusion was measured. (Evaluation criteria) A: The height of the bump was 10 mm or more. B: The height of the rise was 8m or more and less than 10mm. C: The height of the bump was 5 mm or more and less than 8 mm. D: The height of the bump was 2 mm or more and less than 5 mm. E: The height of the bump was less than 2 mm.

[0062] <Evaluation of elevation maintenance> The upper part of the excised pig stomach (the upper part when the entire length was divided into three equal parts) was cut into 5 cm squares to prepare test specimens. 2 mL of each of the endoscopic submucosal injection materials prepared in the Examples and Comparative Examples was injected into the submucosal layer of the test piece using an endoscopic puncture needle (Supergrip, manufactured by Top Corporation, needle diameter 23G). After injecting the endoscopic submucosal injection material into the test piece, it was left to stand for 30 minutes. The height of the raised mucosal layer after standing was measured in the same manner as in the evaluation of the raised property, and evaluated based on the following evaluation criteria. The evaluation results are summarized in Table 1. (Evaluation criteria) A: The difference between the height of the rise immediately after injection and the height of the rise after leaving it to stand for 30 minutes was less than 1 mm. B: The difference in elevation height was 1 m or more and less than 2 mm. C: The difference in uplift height was 2m or more.

[0063] <Easy injection evaluation> A syringe (Terumo Syringe for 5 ml, manufactured by Terumo Corporation) filled with 5 mL of the submucosal injection material for endoscopy prepared in the Examples and Comparative Examples was prepared. The syringe was connected to an endoscopic puncture needle (Supergrip, 23G needle diameter, manufactured by Top Corporation), and the syringe plunger was pressed into the needle at a speed of 100 mm / min using a tensile testing machine (A&D Corporation, benchtop tension / compression testing machine (Force Tester) MCT-2150) to measure the maximum load. The measured maximum load was evaluated based on the following evaluation criteria. The evaluation results are summarized in Table 1. (Evaluation criteria) A: The maximum load was less than 25N. B: The maximum load was 25N or more and less than 50N. C: The maximum load was 50N or more and less than 75N. D: The maximum load was 75N or more and less than 100N. E: The maximum load was 100N or more.

[0064] [Table 1]

[0065] The results in Table 1 show that the submucosal injection materials for endoscopy prepared in the Examples are superior in terms of protuberance, protuberance maintenance, and ease of injection compared to the submucosal injection materials for endoscopy prepared in Comparative Examples 1 to 4. Furthermore, in Comparative Example 5, xanthan gum was denatured by the strong alkaline decomposition treatment, and the aqueous solution containing xanthan gum could not be filtered, making it impossible to prepare a submucosal injection material for endoscopy. However, the polysaccharides A and B satisfying general formula (1) contained in the submucosal injection materials for endoscopy prepared in the Examples were subjected to strong alkaline decomposition treatment, and are therefore found to have excellent suitability for production.

[0066] The disclosure of Japanese Patent Application No. 2021-100417, filed on June 16, 2021, is incorporated herein by reference in its entirety. All documents, patent applications, and technical standards mentioned herein are incorporated herein by reference to the same extent as if each individual document, patent application, and technical standard was specifically and individually indicated to be incorporated by reference.

Claims

1. A submucosal injection material for endoscopy, comprising water and a polysaccharide represented by general formula (1): In general formula (1), R １ , R ２ and R ３ are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or —[CH ２ CH ２－ｋ (CH ３ ) ｋ O] ｍ H, or -CH ２ CH(OH)CH ２ O.C. ｊ H ２ｊ＋１ indicates, n represents an integer from 100 to 100,000; k represents 0 or 1; m represents an integer of 1 to 10, j represents an integer from 6 to 26, The polysaccharide represented by the general formula (1) is a polysaccharide having a —CH ２ CH(OH)CH ２ O.C. ｊ H ２ｊ＋１ has at least one

2. 2. The submucosal injection material for endoscopy according to claim 1, wherein the ratio of the viscosity at a temperature of 25°C and a frequency of 1 Hz to the viscosity at a temperature of 25°C and a frequency of 100 Hz is 10 or more.

3. 3. The submucosal injection material for endoscopy according to claim 1, which has a viscosity of 150 mPa·s or less at a temperature of 25° C. and a frequency of 100 Hz.

4. 3. The submucosal injection material for endoscopy according to claim 1, which has a viscosity of 2000 mPa·s or more at a temperature of 25° C. and a frequency of 1 Hz.

5. 3. The submucosal injection material for endoscopy according to claim 1, wherein j in general formula (1) is an integer of 10 to 20.

6. The submucosal injection material for endoscopy according to claim 1 or 2, wherein the polysaccharide comprises stearylated hydroxypropyl methylcellulose.

7. -CH relative to the mass of the polysaccharide ２ CH(OH)CH ２ O.C. ｊ H ２ｊ＋１ 3. The submucosal injection material for endoscopy according to claim 1, wherein the content of is 0.2% by mass to 1.0% by mass.

8. 3. The submucosal injection material for endoscopy according to claim 1, wherein the content of said polysaccharide relative to the mass of the submucosal injection material for endoscopy is 0.1% by mass to 0.5% by mass.

9. 3. The submucosal injection material for endoscopy according to claim 1, comprising an organic compound having a molecular weight of 400 or less and having two or more hydroxyl groups.

10. The submucosal injection material for endoscopes according to claim 9, wherein the content of the organic compound relative to the mass of the submucosal injection material for endoscopes is 0.1 mass % or more.

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