Hydrogel for treating body cavity injury and body cavity injury treatment kit

Abstract

The hydrogel for treating body cavity injuries is derived from a chitosan derivative in which aldonic acid is bonded to the amino groups of the glucosamine units of chitosan by dehydration condensation. The hydrogel for treating body cavity injuries is granular, and is injected into a body cavity by a syringe for use in treating wounds in the body cavity. The body cavity injury treatment kit includes the syringe, a tube connected to the syringe, and granular hydrogel for treating body cavity injuries filled in the syringe, and the hydrogel for treating body cavity injuries is derived from a chitosan derivative in which aldonic acid is bonded to the amino groups of the glucosamine units of chitosan by dehydration condensation.

Description

[Technical field]

[0001] The present invention relates to a hydrogel for treating a body cavity injury and a kit for treating a body cavity injury. [Background technology]

[0002] Wound dressings are medical materials that cover wounds on the body surface and promote wound healing by keeping them moist. Hydrogel-type wound dressings that contain a large amount of water are suitable for keeping wounds moist. Chitosan has been reported to have a wound healing promoting effect, and chitosan hydrogels are suitable as wound dressings.

[0003] However, highly toxic chemical crosslinkers are widely used to prepare hydrogels from chitosan, and the chitosan hydrogels obtained by such preparations are not suitable for medical use.

[0004] In view of this, a method for preparing a chitosan-derived hydrogel without using additives harmful to living bodies has been proposed (Patent Document 1). In Patent Document 1, a hydrogel that is not toxic to living bodies is prepared by freezing and thawing an aqueous solution containing aldonic acid-modified chitosan.

[0005] Furthermore, Patent Document 2 discloses that a composition containing soluble chitosan or derivatized chitosan is used to treat wounds on the body surface or in a body cavity. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2012 / 105685 [Patent Document 2] Special Publication No. 2013-523827 Summary of the Invention [Problem to be solved by the invention]

[0007] Patent Document 1 is directed to a wound dressing for covering wounds on the body surface, and makes no mention of application to wounds in body cavities.

[0008] The composition of Patent Document 2 is liquid and is orally administered to body cavities such as the paranasal sinuses by spraying, etc. Since this composition is liquid and has fluidity, it flows away even when applied to a wound, and therefore cannot be left in the wound.

[0009] The present invention has been made in consideration of the above-mentioned problems, and an object of the present invention is to provide a hydrogel for treating a body cavity injury and a body cavity injury treatment kit that can also be applied to injuries to a body cavity. [Means for solving the problem]

[0010] The hydrogel for treating a body cavity injury according to the first aspect of the present invention comprises: A hydrogel for treating a body cavity injury, which is derived from a chitosan derivative in which an aldonic acid is bonded to an amino group of a glucosamine unit of chitosan by dehydration condensation, The hydrogel for treating a body cavity injury is Particle size less than 1mm The composition is in granular form and is injected into a body cavity by an injector for use in treating wounds in the body cavity. It is characterized by:

[0012] The aldonic acid is preferably gluconic acid.

[0013] The body cavity may also be the nasal cavity.

[0014] A body cavity injury treatment kit according to a second aspect of the present invention includes: An injector; A tube connected to the injector; Loaded in the syringe Particle size less than 1mm A granular hydrogel for treating a body cavity injury, The hydrogel for treating a body cavity injury is derived from a chitosan derivative in which an aldonic acid is bonded to an amino group of a glucosamine unit of chitosan by dehydration condensation. It is characterized by:

[0015] In addition, the length of the tube is 5 to 15 It is preferable that the length is cm. Effect of the Invention

[0016] According to the present invention, it is possible to provide a hydrogel for treating a body cavity injury and a body cavity injury treatment kit that can also be applied to injuries to a body cavity. [Brief description of the drawings]

[0017] [Figure 1] FIG. 1 shows a synthesis scheme of a chitosan derivative. [Diagram 2] 1 is a graph illustrating the introduction rate of gluconic acid in a chitosan derivative. [Diagram 3] FIG. 2 is a perspective view of a body cavity injury treatment kit. [Figure 4] FIG. 2 is a cross-sectional view of a body cavity injury treatment kit. [Diagram 5] 1 is a photograph of a hydrogel prepared by a freeze-thaw method in an example. [Figure 6] 1 is a photograph of a hydrogel prepared by high-pressure steam sterilization in an example. [Figure 7] 1 is a photograph showing a state in which a hydrogel for treating a body cavity injury is filled into a syringe and ejected from the nozzle. [Figure 8] 1 is a photograph showing the state of a patient's sinuses after endoscopic sinus surgery. [Figure 9] 1 is a photograph showing a state in which a hydrogel for treating a body cavity injury has been injected into a patient's sinus. [Figure 10] 13 is a graph showing the relationship between plunger displacement and injection force. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] <Hydrogel for body cavity injury treatment> The hydrogel for treating a body cavity injury according to the present embodiment is derived from a chitosan derivative in which aldonic acid is bonded to the amino group of the glucosamine unit of chitosan by dehydration condensation. The hydrogel for treating a body cavity injury is granular. The granular hydrogel for treating a body cavity injury can be injected into a body cavity using an injector and used for wound treatment of the body cavity.

[0019] Hydrogels for treating body cavity injuries exert a therapeutic effect on the wound by maintaining a moist environment on the wound surface and promoting cell proliferation when placed on the wound surface. By maintaining a moist environment on the wound surface, the formation of scabs on the wound surface is suppressed, leading to faster healing than with dry wound healing. In addition, since the main component is water, it has a cooling effect and also relieves pain and inflammation.

[0020] Since the hydrogel for treating body cavity injuries is in granular form, it can be filled into a syringe of an injector and ejected from the nozzle of the syringe by pushing out the plunger. Therefore, it is possible to inject and treat a body cavity where it is difficult to treat with a wound dressing material.

[0021] The particle size of the hydrogel for treating a body cavity injury may be such that it can be filled into a syringe of an injector and ejected from the tip of the syringe by pushing out the plunger, and is, for example, 2 mm or less, preferably 1 mm or less. The smaller the particle size of the hydrogel for treating a body cavity injury, the easier it is to fill the injector and eject it from the injector.

[0022] The injector used may be any type capable of injecting the hydrogel for treating body cavity injury, and may be any syringe commonly used in the medical field. Depending on the particle size of the hydrogel for treating body cavity injury used and the body cavity to be treated, a syringe of an appropriate size may be appropriately selected and used, for example, a catheter tip type with a large tip end may be used. In addition, a cylindrical body, such as an extension member or a silicone tube, may be appropriately selected and installed on the tip of the syringe of the syringe for use with the hydrogel for treating body cavity injury.

[0023] The hydrogel for treating body cavity damage can be used, for example, in wound treatment after surgery for sinusitis. Sinusitis is a disease in which the mucous membrane covering the sinuses becomes inflamed for some reason, and surgery is performed when conservative treatment with medication is ineffective. In surgery for sinusitis, an endoscope is used to remove abnormal mucous membranes in the sinuses and open the septa of each sinus, causing the sinuses to become damaged. The hydrogel for treating body cavity damage can be injected and left in place at the damaged site of the sinus using an injector, thereby treating the damaged site.

[0024] Furthermore, the hydrogel for treating injury to a body cavity can be used in any body cavity where injury has occurred, such as the paranasal sinuses, the esophagus, the stomach (stress-induced gastric ulcer), the large intestine, and the like.

[0025] The above-mentioned hydrogel for treating an injury to a body cavity can be produced by granulating a hydrogel prepared by freeze-drying or high-pressure steam sterilization as described below.

[0026] <Preparation of hydrogel by freeze-drying method and production of hydrogel for treating body cavity injury> In the present embodiment, chitosan used to synthesize the chitosan derivative is a deacetylated product of chitin. As is well known, the conversion of chitin to chitosan (deacetylation reaction) does not proceed completely, and some N-acetylglucosamine is contained on the sugar chain. Commercially available chitosan usually has a deacetylation degree in the range of 50 to 100%, and most of them are about 70 to 90%.

[0027] Unless otherwise specified, chitosan used in connection with the present embodiment means chitosan with a deacetylation degree of 50 to 100%, and therefore also includes chitosan with a deacetylation degree of other than 100%.

[0028] The aldonic acid used in synthesizing the chitosan derivative used in the present embodiment is a general term for carboxylic acids obtained by oxidizing monosaccharides and in which the formyl group at the 1-position of aldose is replaced with a carboxyl group, and can be represented, for example, by the following general formula (I): In general formula (I), n is an integer from 2 to 4.

[0029] [ka]

[0030] Aldonic acids suitable for use in the synthesis of the chitosan derivatives used in the present embodiment include gluconic acid, and other suitable aldonic acids include threonic acid and xylonic acid. Furthermore, any carboxylic acid known as an aldonic acid, such as galactonic acid, mannonic acid, lyxonic acid, erythronic acid, ribonic acid, arabinonic acid, allonic acid, altronic acid, gulonic acid, idonic acid, and talonic acid, can be used.

[0031] As can be understood from the above explanation, the chitosan derivative used in the present embodiment can generally be represented as having a repeating unit (repeating unit) consisting of a site where an aldonic acid is bonded to the amino group of a glucosamine unit and a site where an acetylglucosamine unit remains, as shown in the following formula (II): In formula (II), n is an integer of 2 to 4.

[0032] [ka]

[0033] Therefore, when the aldonic acid is gluconic acid, the chitosan derivative used in the present embodiment can generally be represented as having a repeating unit represented by the following formula (III).

[0034] [ka]

[0035] The chitosan derivative used in this embodiment can be synthesized by subjecting aldonic acid to a condensation-dehydration reaction with chitosan to bind (introduce) the aldonic acid to the amino group at the 2-position of the glucosamine unit of chitosan. The aldonic acid is generally reacted as a suitable salt (e.g., Na salt). Figure 1 shows a reaction scheme in the case where gluconic acid is used as the aldonic acid.

[0036] This condensation-dehydration reaction can be carried out at room temperature under acidic conditions using a condensation agent (dehydration condensation agent). Suitable condensation agents for the condensation-dehydration reaction of chitosan and aldonic acid include, but are not limited to, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), which functions to activate the carboxyl group of aldonic acid, and N-hydroxysuccinimide (NHS), which functions to suppress side reactions.

[0037] The introduction rate of aldonic acid such as gluconic acid into chitosan can be adjusted by changing the relative amount of aldonic acid to chitosan and the amount of condensing agent used, and the introduction rate can be increased by increasing the relative amount of aldonic acid and the amount of condensing agent used. The introduction rate of aldonic acid in the chitosan derivative used in this embodiment is, for example, 5 to 60%.

[0038] Here, the introduction rate of aldonic acid such as gluconic acid (into chitosan) is represented by the following formula (A). Aldonic acid introduction rate (%) = [Y / (X+Y)] × 100 (A) X=the amount (moles) of glucosamine units contained in the chitosan-introduced substance, and Y=the amount (moles) of aldonic acid-introduced glucosamine units contained in the chitosan derivative.

[0039] This introduction rate can be calculated by measuring the change in electrical conductivity when an aqueous solution of sodium hydroxide with an equimolar concentration to the hydrochloric acid is added to an aqueous solution of the chitosan derivative (aldonic acid-modified chitosan) dissolved in an appropriate concentration of hydrochloric acid.

[0040] This measurement method is described in detail below with reference to FIG. 2 for gluconic acid-modified chitosan obtained by using gluconic acid as the aldonic acid. When 0.1M sodium hydroxide is added to a 0.1M aqueous solution of gluconic acid-modified chitosan, the H in the solution is neutralized. + The conductivity of the aqueous solution decreases accordingly (Figure 2A-B). When the neutralization reaction is completed, the protonated amino groups in the glucosamine units begin to be deprotonated, and the conductivity does not change until the deprotonation is complete (Figure 2B-C). When the deprotonation is complete, the OH - Since the amount of glucosamine in the glucosamine units increases, the conductivity also increases (Fig. 2C-D). Here, the amount of sodium hydroxide added to the aqueous solution at BC in Fig. 2 corresponds to the amount of protonated amino groups in the glucosamine units. Considering that most of the amino groups in the glucosamine units are protonated in this hydrochloric acid aqueous solution, the amount of sodium hydroxide added to the aqueous solution at BC in Fig. 2 corresponds to the amount of glucosamine units in which gluconic acid is not modified. Therefore, by calculating the amount of glucosamine units in gluconic acid-modified and unmodified chitosan using this measurement method and comparing them, the introduction rate of gluconic acid can be obtained.

[0041] An aqueous solution containing the chitosan derivative (aldonic acid modified chitosan) described above can be poured into a mold (casting die) of a given shape, frozen, and then thawed to obtain a hydrogel of a given shape. The freezing is performed at, for example, -20°C, and the thawing is generally performed at room temperature, but the freezing and thawing temperatures and times are not particularly limited and may be adjusted as necessary.

[0042] The hydrogel prepared as described above is crushed to a predetermined particle size to obtain a hydrogel for treating a body cavity injury. Any method may be used as long as the hydrogel can be crushed into particles, and examples of such methods include a method of crushing using a crusher such as a mixer, a method of crushing using a pestle, and the like.

[0043] Moreover, a hydrogel with improved properties can be formed by mixing the chitosan derivative with polyvinyl alcohol (PVA) and carrying out the same procedure. That is, a hydrogel in which the chitosan derivative is mixed with polyvinyl alcohol is obtained by mixing the aqueous solution containing the chitosan derivative (the aqueous solution to be poured into the mold) with polyvinyl alcohol and then freezing and thawing the mixture.

[0044] When obtaining a hydrogel in which polyvinyl alcohol is mixed with a chitosan derivative, the amount of polyvinyl alcohol in the hydrogel is preferably 1 / 10 or more and less than 2 / 5, more preferably 1 / 5, in terms of chitosan derivative / polyvinyl alcohol [(weight / volume)% ratio]. For example, the hydrogel can be formed with a ratio of chitosan derivative [1 (weight / volume)%] and polyvinyl alcohol [5 (weight / volume)%]. The molecular weight of the polyvinyl alcohol to be applied is 6.6×10 4 Da (Dalton) or more: 2.5 x 10 5 It is preferable to use a value of 1.5×10 Da or less. 5 Da can be used. The molecular weight is 6.6 × 10 4 If the gelation strength is less than 2.5×10 Da, high strength cannot be obtained even if the gelation occurs. 5 If it is larger than Da, the viscosity of the aqueous solution is high and it is difficult to mix the polyvinyl alcohol and the chitosan derivative.

[0045] The hydrogel thus obtained has excellent properties such as excellent strength, water retention, and enzymatic degradation resistance while maintaining high biocompatibility due to the contribution of polyvinyl alcohol. Therefore, when using a hydrogel for treating body cavity injuries using a hydrogel prepared by the freeze-thaw method in an application requiring strength, water retention, and enzymatic degradation resistance, it is preferable to mix polyvinyl alcohol, which can suppress the decrease in gel strength while maintaining biocompatibility and can keep the wound moist for a longer period of time.

[0046] <Preparation of hydrogel by high pressure steam sterilization and production of hydrogel for treating body cavity injury> An aqueous solution containing a chitosan derivative synthesized in the same manner as in the freeze-thaw method described above is placed in a mold (casting die) of a given shape and sterilized by high-pressure steam, whereby the aqueous solution containing the chitosan derivative gels and is sterilized at the same time, forming a biocompatible hydrogel of the given shape.

[0047] High pressure steam sterilization can be performed using an autoclave. The temperature and time for this treatment may be selected so long as sterilization is possible, and may be performed at 2 atm and 121°C or higher for 15 minutes or longer, as in general autoclave sterilization, or may be 20 minutes to 2 hours.

[0048] The high-pressure steam sterilization method has the advantage that a hydrogel can be prepared in a single step, namely, high-pressure steam sterilization of an aqueous solution containing a chitosan derivative, and the hydrogel can be easily prepared even in medical institutions equipped with autoclaves.

[0049] The obtained hydrogel is granulated in the same manner as in the above-mentioned freezing and thawing method to obtain a hydrogel for treating injury to a body cavity. Other matters are the same as those in <Preparation of hydrogel by freeze-drying method and production of hydrogel for treating injury to a body cavity>, so the explanation will be omitted.

[0050] <Body cavity injury treatment kit> As shown in FIGS. 3 and 4, the body cavity injury treatment kit 1 includes a syringe 10, a tube 20, and a hydrogel for treating a body cavity injury filled in the syringe 10.

[0051] The injector 10 comprises a cylindrical syringe 11, a plunger 12, and a cap 13. One longitudinal end of the syringe 11 is completely open, with a flange 11a protruding in the outer diameter direction. A plunger 12 having a piston 12a corresponding to the inner diameter of the syringe 11 is inserted from the opening of the syringe 11. A cylindrical tip 11b protrudes from the other end of the syringe 11. A removable cap 13 is attached to the cylindrical tip 11b.

[0052] The syringe 11 is filled with a hydrogel for treating injury to a body cavity, which is derived from a chitosan derivative in which aldonic acid is bonded to the amino group of the glucosamine unit of the chitosan by dehydration condensation. The plunger 12 is pushed in, the piston 12a is in close contact with the inner wall of the syringe 11, and the tip 11b is plugged with the cap 13, preventing air from entering from the outside. This prevents the hydrogel filled in the syringe 11 from drying out, and allows it to be stored for a long period of time.

[0053] The tube 20 is made of a flexible material such as silicone, etc. The end of the tube 20 is such that the nozzle 11b of the syringe 11 can be inserted therein.

[0054] The injector 10 and the tube 20 may be a commercially available syringe that is generally used in the medical field.

[0055] When using the body cavity injury treatment kit 1, the cap 13 is removed, and one end of the tube 20 is connected to the nozzle 11b. The other end of the tube 20 is then placed against the body cavity to be treated with the hydrogel for treating a body cavity injury, and the plunger 12 is pushed in, whereby the hydrogel for treating a body cavity injury inside the syringe 11 is injected from the tube 20.

[0056] Although there is no limit to the length of the tube 20, if the tube 20 is too short, the hydrogel may not reach the filling site of the body cavity. Also, if the tube 20 is too long, excessive force is required to push the plunger 12. Taking these into consideration, the length of the tube 20 is preferably 5 to 20 cm, and more preferably 5 to 15 cm. EXAMPLES

[0057] <Synthesis of gluconic acid modified chitosan> 3.0 g of chitosan (trade name "Chitosan LL", deacetylation degree 80%, manufactured by Yaizu Suisan Kagaku Kogyo Co., Ltd.) was dissolved in 300 ml of distilled water (pH 4.0) containing 2-morpholinoethanesulfonic acid dissolved at a concentration of 23.5 mM, and the pH was adjusted to 4.0 by adding 1 M aqueous hydrochloric acid. As shown in Table 1, sodium gluconate (hereinafter abbreviated as GA), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (hereinafter abbreviated as EDC), and N-hydroxysuccinimide (hereinafter abbreviated as NHS) were dissolved in this aqueous solution, and the solution was stirred at room temperature for 24 hours to introduce gluconic acid into the amino group at the 2-position of the glucosamine unit of chitosan (see Figure 1 (reaction formula (structural formula))).

[0058] Next, the pH of the reaction solution was adjusted to 8.0 by adding 1M sodium hydroxide aqueous solution, and then 99.5% ethanol was added to precipitate the gluconic acid-modified chitosan and unreacted sodium gluconate, and the precipitate was collected by centrifugation. The precipitate was then enclosed in a dialysis membrane and soaked in distilled water for one week to remove sodium gluconate. The distilled water was replaced twice a day. The precipitate and aqueous solution in the dialysis membrane were then collected, and 99.5% ethanol was added to precipitate the gluconic acid-modified chitosan, and the precipitate was collected. The mixture was then freeze-dried to obtain a dry powder of gluconic acid-modified chitosan.

[0059] The reaction results are shown in Table 1. The gluconic acid introduction rate was calculated by dissolving 0.2 g of gluconic acid-modified chitosan dry powder in 40 ml of 0.1 M aqueous hydrochloric acid solution, and measuring the change in electrical conductivity when 0.1 M aqueous sodium hydroxide solution was added to the solution, as described above.

[0060] [Table 1]

[0061] <Preparation of hydrogels by freezing and thawing> 0.1 g of the synthesized chitosan derivative dry powder with a gluconic acid introduction rate of 18.7% was added to 10 ml of distilled water, and the powder was completely dissolved by adding 0.1 M hydrochloric acid aqueous solution. Next, the pH was adjusted to 7.0 by adding 0.1 M or 1.0 M sodium hydroxide aqueous solution, and the resulting aqueous solution was placed in a metal mold with a star-shaped cross section and frozen at -20°C for 12 hours. After that, it was allowed to stand at room temperature to dissolve, and the formation of a star-shaped gel corresponding to the shape of the metal mold was confirmed, as shown in Figure 5. As a control, gelation was also attempted using chitosan without gluconic acid, but gelation did not occur.

[0062] <Preparation of hydrogel mixed with polyvinyl alcohol> A dry powder of chitosan derivative with a gluconic acid introduction rate of 18.7% was dissolved in physiological saline at pH 4.0 to obtain a 2 (weight / volume)% chitosan derivative solution. 5 The chitosan derivative solution and polyvinyl alcohol solution were mixed at a 1:1 (volume ratio) ratio, and the pH of the solution was adjusted to 7.0 by adding 0.1M or 1.0M sodium hydroxide solution. 1 ml of the resulting solution was placed in a cylindrical container with an inner diameter of 11 mm and frozen at -30°C for 24 hours. The solution was then left to stand at room temperature (20°C) for 2 hours to melt, and the formation of a hydrogel containing polyvinyl alcohol was confirmed.

[0063] <Synthesis of threonic acid-modified chitosan and xylonic acid-modified chitosan and preparation of hydrogel> Threonate-modified chitosan and xylonic acid-modified chitosan were synthesized using threonic acid and xylonic acid as aldonic acids in the same manner as in the synthesis of gluconic acid-modified chitosan described above. The reaction results are shown in Tables 2 and 3 below, respectively. The introduction rate of each aldonic acid was determined by measuring the change in electrical conductivity when an aqueous solution of sodium hydroxide with an equimolar concentration to that of hydrochloric acid was added to an aqueous solution of chitosan derivative (aldonic acid-modified chitosan) dissolved in hydrochloric acid, as described above.

[0064] [Table 2]

[0065] [Table 3]

[0066] The synthesized threonic acid-modified chitosan and xylonic acid-modified chitosan were frozen at -20℃ for 12 hours and then thawed at room temperature using the same method as in <Preparation of hydrogels by freezing and thawing>, and it was confirmed that they gelled.

[0067] <Preparation of hydrogel by high pressure steam sterilization method> The dry powder of gluconic acid-modified chitosan was obtained by the same method as the preparation of hydrogel by the freeze-thaw method described above. The reaction results are shown in Table 4.

[0068] [Table 4]

[0069] The dry powder of each synthesized gluconic acid-modified chitosan was added to distilled water (2.0% [w / v]). The powder was completely dissolved by adding 0.1 M hydrochloric acid. The pH was then adjusted to 7.0 by adding 0.1 M or 1.0 M sodium hydroxide solution.

[0070] The gluconic acid-modified chitosan aqueous solution was placed in a cylindrical glass container with an inner diameter of 15 mm and sealed. This was then placed in an autoclave and subjected to high-pressure steam sterilization (121°C, 2 atm). The processing time was set to 20 minutes, 60 minutes, and 120 minutes, respectively.

[0071] As a result, the aqueous solutions of gluconic acid-modified chitosan gelled and hydrogels were obtained using any of the aqueous solutions of gluconic acid-modified chitosan and for any treatment time. As a representative example, a photograph of the hydrogel obtained using No. 6 is shown in Figure 6.

[0072] <Production of hydrogel for treating body cavity injuries> Each of the hydrogels obtained above was crushed to a particle size of 1 mm or less using a pestle and mortar to obtain hydrogels for treating body cavity injuries. The hydrogels for treating body cavity injuries were then loaded into a syringe and ejected from the nozzle as shown in Figure 7. It was confirmed that all of the hydrogels for treating body cavity injuries could be ejected from the syringe.

[0073] <Treatment for sinusitis> The hydrogel for treating damage to a body cavity filled in a syringe was injected into the sinuses of a patient after endoscopic sinus surgery as shown in Figure 8. The hydrogel for treating damage to a body cavity used was the hydrogel for treating damage to a body cavity obtained using No. 1 above. Figure 9 shows the state in which the hydrogel for treating damage to a body cavity was injected into the sinuses. Since the hydrogel for treating damage to a body cavity is in a gel form, it did not drip out of the sinuses after injection and could be left in place. The wounds healed well after that. The patient did not complain of pain or tingling due to the scabs.

[0074] <Accelerated degradation test of hydrogel for treating body cavity injuries> The hydrogel for treating injury to a body cavity obtained using No. 4 above was subjected to an accelerated deterioration test as follows. The prepared hydrogel for treating body cavity injuries was placed in a container, sealed, and stored at 55° C. until testing. On the day of the test, the hydrogel for treating body cavity injuries was taken out of the container and filled into the syringe. The amount of hydrogel for treating body cavity injuries was 2 mL. The syringe used was made of plastic, with an inner diameter of 12 mm and an inner diameter of 2 mm at the tip. Then, an extrusion test was performed in which the plunger was pushed in at 900 mm / min (15 mm / sec) to eject the hydrogel for treating body cavity injuries from the tip of the cylinder.

[0075] The test dates were the day of manufacture of the hydrogel for treating body cavity injuries, 1 month after manufacture, 2 months after manufacture, 3 months after manufacture, 4 months after manufacture, 5 months after manufacture, and 6 months after manufacture. The relationship between the plunger displacement [mm] and the injection force required for extrusion [N] on each test date is shown in Figure 10.

[0076] Although the injection force tends to increase 4 months after manufacture, it is still strong enough for practitioners to push out the force during actual use. Therefore, it was confirmed that the syringe can be used for about 6 months even if it is filled with hydrogel for treating body cavity injuries and stored.

[0077] The present invention allows various embodiments and modifications without departing from the broad spirit and scope of the present invention. The above-described embodiments are for the purpose of explaining the present invention and do not limit the scope of the present invention. That is, the scope of the present invention is indicated by the claims, not the embodiments. Various modifications made within the scope of the claims and the scope of the invention equivalent thereto are considered to be within the scope of the present invention.

[0078] This application is based on Japanese Patent Application No. 2023-132965 filed on August 17, 2023. The entire specification, claims, and drawings of Japanese Patent Application No. 2023-132965 are incorporated herein by reference. [Industrial Applicability]

[0079] It can be used to treat wounds in body cavities, such as treating wounds in the sinuses after sinus surgery. [Explanation of symbols]

[0080] 1 Body cavity injury treatment kit 10 syringe 11 Syringe 11a Flange 11b Tip of tube 12 Plunger 12a Piston 13 Cap 20 Tubes

Claims

1. A hydrogel for treating a body cavity injury, which is derived from a chitosan derivative in which an aldonic acid is bonded to an amino group of a glucosamine unit of chitosan by dehydration condensation, The hydrogel for treating a wound in a body cavity is in the form of particles having a particle size of 1 mm or less, and is injected into the body cavity by an injector and used for wound treatment in the body cavity. A hydrogel for treating body cavity injuries.

2. The aldonic acid is gluconic acid. The hydrogel for treating a body cavity injury according to claim 1 .

3. The body cavity is the nasal cavity.

3. The hydrogel for treating an injury to a body cavity according to claim 1 or 2.

4. An injector; A tube connected to the injector; A granular hydrogel for treating a body cavity injury having a particle size of 1 mm or less filled in the injector, The hydrogel for treating a body cavity injury is derived from a chitosan derivative in which an aldonic acid is bonded to an amino group of a glucosamine unit of chitosan by dehydration condensation. A body cavity injury treatment kit comprising:

5. The length of the tube is 5 to 15 cm.

5. The body cavity injury treatment kit according to claim 4.

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