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

Abstract

This hydrogel for body cavity injury treatment is derived from a chitosan derivative in which an aldonic acid is bonded by dehydration condensation to an amino group of a glucosamine unit of chitosan. The hydrogel for body cavity injury treatment is granular, the hydrogen being injected into a body cavity by an injector and being used for wound treatment in a body cavity. This body cavity injury treatment kit comprises an injector, a tube connected to the injector, and a granular hydrogel for body cavity injury treatment that is filled into the injector. The hydrogel for body cavity injury treatment is derived from a chitosan derivative in which an aldonic acid is bonded by dehydration condensation to an amino group of a glucosamine unit of chitosan.

Description

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

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

[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 containing a large amount of water are suitable for maintaining a moist wound. Chitosan has been reported to have the effect of promoting wound healing, and chitosan hydrogels are suitable for use 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 this document, a non-biologically toxic hydrogel 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.

[0006] International Publication No. 2012 / 105685 Special Publication No. 2013-523827

[0007] Patent Document 1 is directed to a wound dressing for covering wounds on the body surface, and does not disclose any 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. Because this composition is liquid and fluid, it flows away even when applied to a wound, and therefore cannot be left in place on the wound.

[0009] The present invention has been made in view of the above circumstances, 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.

[0010] A hydrogel for treating a body cavity injury according to a first aspect of the present invention is a hydrogel for treating a body cavity injury derived from a chitosan derivative in which aldonic acid is bonded to the amino group of a glucosamine unit of chitosan by dehydration condensation, and is characterized in that the hydrogel for treating a body cavity injury is in a granular form, is injected into a body cavity by an injector, and is used to treat a wound in the body cavity.

[0011] Furthermore, it is preferable that the particle size of the hydrogel for treating an injury to a body cavity is 2 mm or less.

[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 comprises an injector, a tube connected to the injector, and a granular body cavity injury treatment hydrogel filled in the injector, wherein the body cavity injury treatment hydrogel is derived from a chitosan derivative in which aldonic acid is bonded to the amino group of a glucosamine unit of chitosan by dehydration condensation.

[0015] It is also preferable that the length of the tube is 5 to 20 cm.

[0016] According to the present invention, 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 can be provided.

[0017] 1 is a diagram showing a synthesis scheme for a chitosan derivative; FIG. 2 is a graph illustrating the introduction rate of gluconic acid in a chitosan derivative; FIG. 3 is a perspective view of a kit for treating a body cavity injury; FIG. 4 is a cross-sectional view of a kit for treating a body cavity injury; FIG. 5 is a photograph of a hydrogel prepared by a freezing and thawing method in an example; FIG. 6 is a photograph of a hydrogel prepared by high-pressure steam sterilization in an example; FIG. 7 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; FIG. 8 is a photograph showing the state of a patient's sinuses after endoscopic sinus surgery; FIG. 9 is a photograph showing a state in which a hydrogel for treating a body cavity injury has been injected into a patient's sinuses; and FIG. 10 is a graph showing the relationship between plunger displacement and injection force.

[0018] <Hydrogel for treating body cavity injury> The hydrogel for treating body cavity injury according to this 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 body cavity injury is granular. The granular hydrogel for treating body cavity injury can be injected into a body cavity using a syringe and used to treat wounds in the body cavity.

[0019] Hydrogels for treating body cavity injuries exert a therapeutic effect on the wound surface by maintaining a moist environment on the wound surface and promoting cell proliferation when placed on the wound surface. Maintaining a moist environment on the wound surface prevents scab formation and leads to faster healing than with dry wound healing. In addition, because the main component is water, it has a cooling effect, which 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 injected from the nozzle of the syringe by pushing the plunger, making it possible to inject and treat body cavities that are difficult to treat with wound dressings.

[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 injected from the nozzle 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 to inject it from the injector.

[0022] The injector used may be any type capable of injecting the hydrogel for treating a body cavity injury, and any syringe commonly used in the medical field may be used. A syringe of an appropriate size may be selected and used depending on the particle size of the hydrogel for treating a body cavity injury used and the body cavity to be treated. For example, a catheter tip type syringe with a large tip may be used. Furthermore, a cylindrical member, such as an extension member or a silicone tube, may be selected and attached to the tip of the syringe barrel of the syringe, and used accordingly for the body cavity to be treated with the hydrogel for treating a body cavity injury.

[0023] The hydrogel for treating body cavity injuries can be used, for example, to treat wounds after surgery for sinusitis. Sinusitis is a disease in which the mucous membranes lining the sinuses become inflamed for some reason, and surgery is performed when conservative treatment with medication is ineffective. During sinusitis surgery, an endoscope is used to remove abnormal mucous membranes within the sinuses and open the septa of each sinus, causing damage to the sinuses. The damaged area can be treated by injecting and leaving the hydrogel for treating body cavity injuries at the damaged site of the sinus using an injector.

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

[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 follows.

[0026] <Preparation of Hydrogel by Freeze-Drying Method and Production of Hydrogel for Treating Body Cavity Injuries> In this embodiment, chitosan used to synthesize chitosan derivatives 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 in the sugar chain. Commercially available chitosan usually has a deacetylation degree in the range of 50 to 100%, with most being around 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 includes chitosan with a deacetylation degree of less than 100%.

[0028] The aldonic acid used to synthesize the chitosan derivative used in this embodiment is a general term for carboxylic acids obtained by oxidizing monosaccharides, 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 of 2 to 4.

[0029]

[0030] Examples of aldonic acids suitable for use in synthesizing the chitosan derivatives used in this embodiment include gluconic acid, and other suitable aldonic acids include threonic acid and xylonic acid. Furthermore, any of the carboxylic acids known as aldonic acids, 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 also 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 bound 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]

[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]

[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 for 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 condensing agent (dehydration condensing agent). Suitable condensing agents for the condensation-dehydration reaction of chitosan with 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 expressed by the following formula (A): Aldonic acid introduction rate (%) = [Y / (X+Y)] × 100 (A), where X = the amount (number of moles) of glucosamine units contained in the chitosan-introduced product, and Y = the amount (number of moles) of aldonic acid-introduced glucosamine units contained in the chitosan derivative.

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

[0040] This measurement method is explained in detail with reference to Figure 2 for gluconic acid-modified chitosan obtained by using gluconic acid as the aldonic acid. When 0.1 M sodium hydroxide is added to a 0.1 M aqueous solution of hydrochloric acid in which gluconic acid-modified chitosan is dissolved, the H ＋The conductivity of the aqueous solution decreases accordingly (Fig. 2A-B). When the neutralization reaction is complete, the protonated amino groups in the glucosamine units begin to be deprotonated, and the conductivity remains constant until the deprotonation is complete (Fig. 2B-C). When the deprotonation is complete, the OH － As the amount of glucosamine in the glucosamine unit increases, the conductivity also increases (Figures 2C-D). The amount of sodium hydroxide added to the aqueous solution at points B-C in Figure 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 points B-C in Figure 2 corresponds to the amount of glucosamine units not modified with gluconic acid. Therefore, by calculating the amount of glucosamine units in gluconic acid-modified and unmodified chitosan using this measurement method and comparing the results, the introduction rate of gluconic acid can be determined.

[0041] A hydrogel having a desired shape can be obtained by pouring an aqueous solution containing the chitosan derivative (aldonic acid-modified chitosan) into a mold (casting die) of a desired shape, freezing it, and then thawing it. The freezing is performed at, for example, −20° C., and the thawing is generally performed at room temperature. However, the freezing and thawing temperatures and times are not particularly limited and may be adjusted as needed.

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

[0043] Furthermore, 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, by mixing polyvinyl alcohol with an aqueous solution containing the chitosan derivative (aqueous solution to be poured into a mold) and then freezing and thawing the mixture, a hydrogel containing the chitosan derivative and polyvinyl alcohol can be obtained.

[0044] When obtaining a hydrogel in which a chitosan derivative is mixed with polyvinyl alcohol, 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 the chitosan derivative / polyvinyl alcohol (weight / volume %) ratio. For example, the hydrogel can be formed with a chitosan derivative / polyvinyl alcohol ratio of 1 (weight / volume %) to 5 (weight / volume %). The molecular weight of the polyvinyl alcohol used is preferably 6.6×10 in consideration of the ease of gel formation. ４ Da (Dalton) or more 2.5 x 10 ５ It is preferable to use one having a molecular weight of 1.5 × 10 Da or less. ５ A molecular weight of 6.6 x 10 Da can be used. ４ If the viscosity is smaller than 2.5 × 10 Da, high strength cannot be obtained even after gelation. ５ If it is larger than Da, the viscosity of the aqueous solution is high, making it difficult to mix the polyvinyl alcohol and the chitosan derivative.

[0045] The hydrogel obtained in this manner maintains high biocompatibility while exhibiting excellent properties such as excellent strength, water retention, and enzymatic degradation resistance, thanks 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 prevents a decrease in gel strength while maintaining biocompatibility and enables the wound to be kept moist for a longer period of time.

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

[0047] High-pressure steam sterilization can be performed using an autoclave. The temperature and time for this treatment may be selected so as to enable sterilization, and similarly to general autoclave sterilization, the treatment may be performed at 2 atmospheres and 121°C or higher for 15 minutes or more, or may be 20 minutes to 2 hours.

[0048] The high-pressure steam sterilization method has the advantage that the hydrogel can be prepared in a single step, namely, by 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 can be granulated in the same manner as in the freeze-thawing method described above to obtain a hydrogel for treating a body cavity injury. Other details are the same as in <Preparation of a hydrogel by freeze-drying method and production of a hydrogel for treating a body cavity injury>, and therefore will not be described here.

[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 includes 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 extending radially outward. A plunger 12 having a piston 12a corresponding to the inner diameter of the syringe 11 is inserted through 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 body cavity injuries, which 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. When the plunger 12 is pushed in, the piston 12a is in close contact with the inner wall of the syringe 11, and the nozzle 11b is closed with the cap 13. This prevents air from entering from the outside, thereby preventing the hydrogel filled in the syringe 11 from drying out and enabling long-term storage.

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

[0054] The injector 10 and the tube 20 may be commercially available syringes that are commonly 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 body cavity injury treatment, and the plunger 12 is pushed in, thereby injecting the hydrogel for body cavity injury treatment from the syringe 11 through 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 point in the body cavity. Also, if the tube 20 is too long, excessive force is required to push the plunger 12. Taking these factors into consideration, the length of the tube 20 is preferably 5 to 20 cm, and more preferably 5 to 15 cm.

[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 23.5 mM 2-morpholinoethanesulfonic acid, 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 mixture 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 1 M aqueous sodium hydroxide, and then 99.5% ethanol was added to precipitate the gluconic acid-modified chitosan and unreacted sodium gluconate. The precipitate was then collected by centrifugation. The precipitate was then sealed in a dialysis membrane and immersed in distilled water for one week to remove the 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. The precipitate was then collected. A dry powder of gluconic acid-modified chitosan was obtained by freeze-drying.

[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 conductivity when 0.1 M aqueous sodium hydroxide solution was added to the solution, as described above.

[0060]

[0061] Preparation of Hydrogels by Freezing and Thawing: 0.1 g of the synthesized dry powder of chitosan derivative with an 18.7% gluconic acid content was added to 10 ml of distilled water, and 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. The resulting solution was placed in a metal mold with a star-shaped cross section and frozen at -20°C for 12 hours. After allowing to dissolve at room temperature, a star-shaped gel was formed, conforming to the shape of the metal mold, as shown in Figure 5. As a control, gelation was also attempted using chitosan without gluconic acid, but no gelation occurred.

[0062] <Preparation of hydrogel containing 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 (wt / vol)% chitosan derivative solution. In addition, polyvinyl alcohol powder (molecular weight 1.5 × 10) was dissolved in another physiological saline solution. ５The chitosan derivative solution and polyvinyl alcohol solution were mixed at a 1:1 (volume ratio) ratio, and 0.1 M or 1.0 M aqueous sodium hydroxide solution was added to adjust the pH of the solution to 7.0. 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 thaw at room temperature (20°C) for 2 hours, confirming the formation of a hydrogel containing polyvinyl alcohol.

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

[0064]

[0065]

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

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

[0068]

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

[0070] The gluconic acid-modified chitosan solution was placed in a cylindrical glass container with an inner diameter of 15 mm, sealed, and then placed in an autoclave for high-pressure steam sterilization (121°C, 2 atmospheres) for 20, 60, or 120 minutes.

[0071] As a result, regardless of the preparation time and the amount of gluconic acid-modified chitosan solution used, the aqueous solution gelled to form a hydrogel. A representative photograph of the hydrogel obtained using No. 6 is shown in Figure 6.

[0072] <Production of Hydrogels for Treating Injuries to a Body Cavity> 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 injuries to a body cavity. The hydrogels for treating injuries to a body cavity were then filled into a syringe and ejected from the nozzle, as shown in Figure 7. It was confirmed that all of the hydrogels for treating injuries to a body cavity could be ejected from the syringe.

[0073] <Treatment of Sinusitis> A hydrogel for treating a body cavity injury 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 a body cavity injury used was the hydrogel for treating a body cavity injury obtained using No. 1 above. Figure 9 shows the state of the hydrogel for treating a body cavity injury injected into the sinus. Because the hydrogel for treating a body cavity injury is in gel form, it did not drip out of the sinus after injection and could be left in place. The wound subsequently healed well. Furthermore, the patient did not complain of pain or tingling due to the scabs.

[0074] <Accelerated Degradation Test of Hydrogel for Treating Body Cavity Injury> An accelerated degradation test was conducted as follows using the hydrogel for treating body cavity injury obtained using No. 4 above. The produced hydrogel for treating body cavity injury was placed in a sealed container and stored at 55°C until testing. On the day of testing, the hydrogel for treating body cavity injury was removed from the container and filled into a syringe. The filled volume of the hydrogel for treating body cavity injury was 2 mL. The syringe used was made of plastic, with an inner diameter of 12 mm and an inner diameter of the nozzle of 2 mm. An extrusion test was then conducted in which the plunger was pushed in at 900 mm / min (15 mm / sec) to eject the hydrogel for treating body cavity injury from the nozzle.

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

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

[0077] The present invention allows various embodiments and modifications without departing from the broad spirit and scope of the present invention. Furthermore, the above-described embodiments are intended to explain the present invention and do not limit the scope of the present invention. That is, the scope of the present invention is defined by the claims, not the embodiments. Various modifications made within the scope of the claims and the meaning 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.

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

[0080] 1 Body cavity injury treatment kit 10 Injector 11 Syringe 11a Flange 11b Nozzle 12 Plunger 12a Piston 13 Cap 20 Tube

Claims

1. A hydrogel for treating an injury to a body cavity, which is derived from a chitosan derivative in which aldonic acid is bonded to the amino group of a glucosamine unit of chitosan by dehydration condensation, said hydrogel for treating an injury to a body cavity being in a granular form, which is injected into a body cavity by an injector and used to treat a wound in said body cavity.

2. The hydrogel for treating an injury to a body cavity according to claim 1, characterized in that the particle size of the hydrogel for treating an injury to a body cavity is 2 mm or less.

3. The hydrogel for treating a body cavity injury according to claim 1, characterized in that the aldonic acid is gluconic acid.

4. The hydrogel for treating an injury to a body cavity according to any one of claims 1 to 3, characterized in that the body cavity is a nasal cavity.

5. A kit for treating an injury to a body cavity comprising: a syringe; a tube connected to the syringe; and a granular hydrogel for treating an injury to a body cavity filled in the syringe, wherein the hydrogel for treating an injury to a body cavity 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.

6. The body cavity injury treatment kit according to claim 5, wherein the length of the tube is 5 to 20 cm.

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