JP7169104B2 - lacrimal tube - Google Patents

Description

The present invention relates to lacrimal tubes.

Tears are discharged from the punctum at the inner corner of the eye through the lacrimal ducts into the nostrils. When this lacrimal duct is blocked, tears overflow, resulting in lacrimation (watery eyes).

Therefore, as a method of treating epiphora, there is a method of opening the blocked lacrimal duct and indwelling a lacrimal tube (see, for example, Patent Document 1) for 1 to 3 months in order to stabilize the lesion.

Japanese Patent No. 5999109

If the lesion in the lacrimal duct is not stabilized, re-obstruction may occur, and re-indwelling of the lacrimal duct tube or surgical operation may be required. Nothing but room for improvement.

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a lacrimal duct tube capable of obtaining a high therapeutic effect on the lacrimal duct and suppressing reocclusion.

The present inventors have found that placing an anti-inflammatory agent or an epithelial cell growth promoting agent in the lacrimal tube can provide a high therapeutic effect on the lacrimal duct, and have completed the present invention. More specifically, the present invention provides the following.

(1) A lacrimal tube in which an anti-inflammatory agent or an epithelial cell growth promoting agent is at least partially disposed.

(2) The lacrimal tube according to (1), wherein the anti-inflammatory agent or epithelial cell growth promoting agent is rebamipide or an analogue thereof.

(3) The lacrimal tube according to (1) or (2), wherein the anti-inflammatory agent or the epithelial cell growth promoting agent is placed inside the lacrimal tube.

(4) Equipped with a bougie hole,
The lacrimal tube according to (1) or (2), wherein the anti-inflammatory agent or the epithelial cell growth promoting agent is placed on the opposite side of the bougie hole from the bougie insertion direction and inside the lacrimal tube.

(5) The lacrimal tube according to any one of (1) to (4), wherein the anti-inflammatory agent or epithelial cell growth promoting agent is dispersed in a resin.

(6) The lacrimal tube according to (5), wherein the resin is a biodegradable polymer.

(7) The lacrimal tube according to (5) or (6), wherein the mass of the anti-inflammatory agent or the epithelial cell growth promoter is 60% by mass or less with respect to the resin.

(8) The lacrimal tube according to any one of (5) to (7), wherein the mass of the anti-inflammatory agent or the epithelial cell growth promoter is 35% by mass or less with respect to the resin.

(9) The lacrimal tube according to any one of (1) to (8), wherein the anti-inflammatory agent or epithelial cell growth promoting agent can be continuously released for 30 days or longer.

ADVANTAGE OF THE INVENTION According to this invention, the high therapeutic effect of a lacrimal duct can be acquired and the lacrimal duct tube which can suppress reocclusion can be provided.

FIG. 1 shows one embodiment of the lacrimal tube of the present invention; 1 is a schematic diagram of the anatomical structure of a lacrimal duct; FIG. FIG. 2 is an enlarged cross-sectional view of A in FIG. 1 as seen from the right side of the paper, showing an embodiment in which the lacrimal tube has a bougie hole; FIG. 2 is an enlarged cross-sectional view of A in FIG. 1 viewed from the right side of the paper surface, and is a view of an embodiment in which the lacrimal tube has a bougie hole and a communication hole. FIG. 2 is an enlarged cross-sectional view of A in FIG. 1 viewed from the right side of the paper surface, and is a diagram of an embodiment in which the lacrimal tube has a bougie hole, a communication hole, and a flow control valve. 1 shows an observed image of the lacrimal duct when the tube of Comparative Example 1 is placed in the left lacrimal duct of a rabbit, and an observed image of the lacrimal duct when the tube of Example 2 is placed in the right lacrimal duct of the same rabbit. 1 shows an observed image of the lacrimal duct when the tube of Comparative Example 1 is placed in the left lacrimal duct of a rabbit, and an observed image of the lacrimal duct when the tube of Example 1 is placed in the right lacrimal duct of the same rabbit. In the observation image shown in FIG. 6, an analysis image is shown in which the blue portion stained with toluidine blue is displayed in black. In the observed image shown in FIG. 7, an analysis image is shown in which the blue portion stained with toluidine blue is displayed in black. FIG. 4 is a graph showing residual coating over time when the lacrimal tubes of Examples 3-5 were subjected to sustained release testing. FIG.

Embodiments of the present invention will be described below, but the present invention is not particularly limited to these and can be modified as appropriate.

The present invention is a lacrimal tube having an anti-inflammatory agent or an epithelial cell growth promoting agent disposed in at least a portion thereof. First, one embodiment of the lacrimal duct tube of the present invention will be described with reference to the drawings. In the present invention, the term "lacrimal tube" refers to a tube that is left in the lacrimal duct.

In the present invention, the lacrimal duct refers to, as shown in FIG. , nasolacrimal duct (27), nasal duct (not shown), and Hasner's valve (not shown). ) leading to the eye (ocular appendage). FIG. 2 schematically shows the anatomical structure of the lacrimal duct. The upper lacrimal duct (28) is the tube leading from the upper lacrimal punctum (21) through the upper canaliculus (23) and the common lacrimal canaliculus (25) to the inferior nasal meatus (28). The canaliculus (24), the common canaliculus (25), and leading to the inferior meatus (28) are called the inferior lacrimal duct.

In this embodiment, the lacrimal tube is an integral tube that is placed in the lacrimal duct. Here, "integrated" means that the two tubes inserted respectively into the upper/lower lacrimal ducts are integrated as one. Also, the integral tube means a flexible intubation device having a predetermined length inserted for the purpose of reconstructive treatment of the lacrimal duct. Specifically, as shown in FIG. 1 , the lacrimal tube in this embodiment is a nunchuk-type lacrimal tube that includes a central portion 4 and a cylindrical portion 5 . Further, in the present embodiment, the tubular portion 5 is composed of a first tubular portion 5a and a second tubular portion 5b.

The central portion 4 connects the first tubular portion 5a and the second tubular portion 5b. A substantially central portion of the central portion 4 is a site to be indwelled in the punctum, canaliculus, common canaliculus, and lacrimal sac. The shape of the central portion 4 is not particularly limited, and may be cylindrical or rod-shaped, for example. In addition, the central portion 4 is provided with a midpoint 3 at a position substantially in the center of the nunchuk-type lacrimal tube, which facilitates confirmation of the insertion position and the indwelling position. In addition, in the present embodiment, the central portion 4 is formed thinner than the first tubular portion 5a and the second tubular portion 5b to form a so-called nunchuk type, but the present invention is not particularly limited to this type. .

The first tubular portion 5a is connected to one end of the central portion 4 and serves as a portion to be indwelled in the lacrimal sac, nasolacrimal duct, Hasner's valve, and inferior nasal meatus.

The second tubular portion 5b is connected to the other end of the central portion 4 and serves as a portion to be placed in the lacrimal sac, nasolacrimal duct, Hasner's valve, and inferior nasal meatus.

The shapes of the first tubular portion 5a and the second tubular portion 5b are not particularly limited as long as they can be indwelled in the lacrimal duct, but in this embodiment, they are tubular. Further, in this embodiment, the first end 6 of the first cylindrical portion 5a and the second end 8 of the second cylindrical portion 5b are blind ends, and the ends thereof are sharp. Also, in this embodiment, the tip portion including the first end 6 is colored so that the operator can easily distinguish the tip portion including the second end 8 from the tip portion including the second end 8 . Further, in this embodiment, two marks 9a are provided at predetermined positions from the first end 6 of the first tubular portion 5a so that the operator can visually recognize the insertion depth. The second tubular portion 5b is similarly provided with a mark 9b.

In the present embodiment, the sidewalls of the first cylindrical portion 5a and the second cylindrical portion 5b near the central portion 4 are provided with bougie holes (cuts for inserting bougies) 7 (the first bougie hole 7a and the second bougie hole 7a, respectively). Two bougie holes 7b) are provided. As shown in FIG. 1, a first bougie 2a and a second bougie 2b as insertion aids are inserted through the first bougie hole 7a and the second bougie hole 7b into the first cylindrical portion 5a and the second cylindrical portion 5a, respectively. It can be inserted through the hollow portion of the portion 5b. The structures of the first bougie hole 7a and the second bougie hole 7b are not particularly limited, and may be structures such as small holes and cuts. Note that the bougie hole may be used to insert not only the bougie but also the lacrimal endoscope.

In this embodiment, openings are formed at both ends of the cylindrical portion 5 of the tube. Since the opening is provided in the tubular portion 5 in this manner, it is possible to secure a visual field and to conduct a water flow test from the lacrimal endoscope through this opening. As the structure of the cylindrical portion 5 of the tube in this embodiment, for example, a cylindrical shape having openings formed at both ends and communicating with each other in a hollow portion can be mentioned. However, it is not necessary to form openings at both ends of the cylindrical portion 5 of the tube. Further, the cylindrical shape may have substantially constant inner and outer diameters over the entire length.

In addition, as another example of the structure of the integral tube as in this embodiment, the central portion 4 of the tube has a rod-shaped portion, and each end has an opening on both sides thereof, and the opening and a cylindrical portion having a hollow portion that communicates with. In this case, the outer diameter may be substantially constant over the entire length of the integrated tube, or the central rod-shaped portion may have a substantially constant small diameter portion.

The shape of the distal end of the tubular portion 5 in this embodiment is not particularly limited, but from the viewpoint of preventing damage to the lacrimal duct, it is preferably a shape without edges. For example, the external shape of the end portion may be a non-sharp shape such as a substantially conical or pyramidal shape, a shape in which the end face of the end portion is chamfered, or a rounded shape, but is not limited to these.

In this embodiment, the central portion 4 may have a substantially constant small diameter portion. Further, in the above-exemplified embodiment, when the central portion 4 has a substantially constant small diameter portion, at least two portions of the tubular portion 5 that are indwelled from the lacrimal sac into the nasolacrimal duct are Alternatively, the portion from the punctum to the canaliculus may be rod-shaped. A lacrimal duct tube in which the cylindrical portion 5 has such a shape and structure, and the central portion 4 is more flexible than both side portions thereof, is called a so-called nunchuk-type lacrimal duct tube, as described above. A nunchaku-type lacrimal tube means a lacrimal tube named because its shape resembles that of a nunchaku used in Chinese martial arts. Preferably, the central portion is flexible enough to form an inverted U shape when supported at the center point of the length of the tube and lifted.

The insertion aid in the present invention refers to a device that guides the lacrimal tube into the lacrimal duct while it is inserted into the lacrimal duct and then removes it when the lacrimal tube is inserted into and left in the lacrimal duct. For example, the bougie in FIG. 1 corresponds to this. In addition, when inserting while observing the inside of the lacrimal duct visually, a lacrimal endoscope is used instead of the bougie, and such an endoscope also corresponds to the insertion aid.

The constituent materials (materials) of the cylindrical portion 5 and the central portion 4 in the tube of the present invention are not particularly limited, and examples thereof include resin compositions containing silicone, polyurethane, isobutylene-based copolymers, and alloys thereof. . As the alloy, for example, when an alloy of a thermoplastic polyurethane resin and an isobutylene copolymer is used, the proportion of the isobutylene copolymer (A) and the thermoplastic polyurethane resin (B) is adjusted. You can adjust the hardness of the tube. As the ratio of the thermoplastic polyurethane resin (B) is set higher, the hardness of the tube can be increased. From the viewpoint of antithrombogenicity, surface slipperiness, and flexibility, it is preferable that the isobutylene-based copolymer (A) is contained in an amount of 1% by weight or more (i.e., the isobutylene-based copolymer (A) and The ratio of the thermoplastic polyurethane resin (B) is (A)/(B)=1/99 to 99/1 by weight. Among them, from the viewpoint of abrasion resistance, the weight ratio of the isobutylene-based copolymer (A) and the thermoplastic polyurethane-based resin (B) is (A)/(B)=1/99 to 70/30. is preferably In particular, from the viewpoint of compressive stress, the weight ratio of the isobutylene-based copolymer (A) and the thermoplastic polyurethane-based resin (B) is (A)/(B)=1/99 to 50/50. Preferably. The resin composition for the one-piece tube used in the present invention may consist of only the isobutylene copolymer (A) and the thermoplastic polyurethane resin (B), or may be mixed with other components.

As the isobutylene-based copolymer (A), "SIBSTAR (registered trademark) 102T" manufactured by Kaneka Corporation, which is a styrene-isobutylene-styrene block copolymer (hereinafter sometimes referred to as SIBS), is preferable. As the thermoplastic polyurethane resin (B) (hereinafter sometimes referred to as TPU), "Miractran E385PNAT" manufactured by Nippon Miractran Co., Ltd., "Tecotan TT1074A" manufactured by Lubrizol, which is an ether-based aromatic cyclic polyurethane, or ether-based alicyclic Polyurethane such as “Tecoflex EG100A” and “Tecoflex EG85A” manufactured by Lubrizol, or polycarbonate polyurethane such as “Carbotan PC3575A” manufactured by Lubrizol is preferable.

In at least some of the above-described lacrimal tubes of the present invention, an anti-inflammatory agent or epithelial cell growth promoting agent is disposed in the lacrimal tube.

The place where the anti-inflammatory agent or epithelial cell growth promoting agent is placed is not particularly limited, and for example, it may be placed inside or on the surface of the lacrimal tube, but it is preferably placed inside the lacrimal tube. Inside the lacrimal tube, for example, FIG. 3 is an enlarged cross-sectional view of one embodiment of the portion A in FIG. The first coating region R1 located on the side opposite to the direction (hereinafter referred to as the “bougie insertion direction”) D, and the second coating region R2 located on the bougie insertion direction D side with respect to the bougie hole 7 are exemplified. be done. Tears tend to flow slower when flowing inside the lacrimal tube than when flowing on the surface of the lacrimal tube. This is because tears must enter and leave the bougie hole when flowing inside the lacrimal tube. Therefore, the release rate of the anti-inflammatory agent or epithelial cell growth-promoting agent placed inside the lacrimal tube tends to be slow, and the release period of the anti-inflammatory agent or epithelial cell growth-promoting agent can be set for a long period of time. Easy to design for release. Also, the residence time of tears is longer inside the lacrimal tube than on the surface of the lacrimal tube. As a result, the anti-inflammatory agent or epithelial cell growth promoter has a longer contact time with tears and an increased concentration in tears when placed inside the lacrimal tube rather than placed on the surface of the lacrimal tube. Cheap. Thus, placing an anti-inflammatory agent or epithelial cell growth-promoting agent inside the lacrimal tube, e.g., one or both of the first coating region R1 and the second coating region R2, results in treatment with the anti-inflammatory agent or epithelial cell growth-promoting agent. Efficacy can be improved easily. By placing an anti-inflammatory agent or an epithelial cell growth promoting agent in the first coating region R1, tears temporarily accumulate in R1 when tears pass through, and at that time, the anti-inflammatory agent or epithelial cell growth promoting agent is applied to tears. Since it flows together, a high reocclusion suppression effect can be obtained. Therefore, the anti-inflammatory agent or epithelial cell growth promoting agent is preferably arranged in the first coating region R1. The surface of the lacrimal tube includes, for example, a third coating region R3 located on the surface of the lacrimal tube, as shown in FIG.

Anti-inflammatory agents include prostaglandin production promoters (rebamipide, misoprostol, analogues thereof, etc.), sucralfate, sodium alginate, steroids (flumetholone, rinderone, etc.) and the like. Among these, rebamipide or its analogues are preferred.

Epithelial cell growth promoters include epithelial healing promoters such as rebamipide, tranilast, and analogues thereof. Among these, rebamipide or its analogues are preferred.

Analogues of rebamipide include, for example, teprenone (trade name Selvex®).

In the present invention, the active ingredient of the anti-inflammatory agent or epithelial cell growth promoter may be used singly or in combination of two or more. Examples of a mode in which two or more active ingredients are used in combination include a mode in which rebamipide is placed inside a tube and steroid is placed on the surface of the tube.

The anti-inflammatory agent or epithelial cell growth promoting agent is preferably dispersed in the resin. By dispersing in the resin in this way, the release rate of the anti-inflammatory agent or epithelial cell growth promoting agent becomes slow, and sustained release can be obtained. Specific examples of resins that can be used include polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene, fluorinated ethylene propylene copolymer, polyvinyl acetate, polystyrene, poly(ethylene terephthalate), polyurethane, polyurea, and silicone. Polymers such as rubbers, polyamides, polycarbonates, polyaldehydes, polyester copolymers, styrene-butadiene copolymers, styrene-isobutylene copolymers, polyvinylpyrrolidone, maleic anhydride polymers, or copolymers of two or more thereof, or two of these A mixture of the above may be mentioned. As the resin, it is also preferable to use biodegradable plastics such as polylactic acid, polyglycolic acid, polycaprolactone, polybutylene succinate, polybutylene adipate, polyethylene succinate, and cellulose ester.

In the present invention, the mass of the anti-inflammatory agent or epithelial cell growth promoter is not particularly limited. % by mass or less, for example, 0.1 to 60% by mass). However, from the viewpoint of the shape retention of the mixture of the resin and the anti-inflammatory agent or epithelial cell growth promoting agent, and because a higher sustained release can be obtained, the mass of the anti-inflammatory agent or epithelial cell growth promoting agent is The content of the resin is preferably 50% by mass or less, more preferably 40% by mass or less, even more preferably 35% by mass or less, further preferably 30% by mass or less, and 25% by mass. It is more preferably 20% by mass or less, and particularly preferably 15% by mass or less. In these cases, the lower limit of the mass is not particularly limited, and may be greater than 0% by mass or 0.1% by mass or more.

As a method of dispersing the anti-inflammatory agent or epithelial cell growth promoting agent in a resin and disposing it in the lacrimal tube, for example, the anti-inflammatory agent or epithelial cell growth promoting agent is added to a resin solution obtained by dissolving the resin in a solvent. Then, the resulting liquid mixture is applied to the site where the anti-inflammatory agent or epithelial cell growth promoting agent is to be placed, and then dried to form a coating. Also, a method of preparing in advance a member containing a mixture of an anti-inflammatory agent or an epithelial cell growth promoting agent and a resin and arranging this member in the lacrimal tube is applicable.

In the present invention, the anti-inflammatory agent or epithelial cell growth promoting agent is preferably configured to be continuously released over a long period of time throughout the period in which inflammation exists and the period in which epithelial cells are repaired. It is preferably configured to be continuously released for 1 day or more, 10 days or more, 15 days or more, 30 days or more, or 60 days or more. In humans, the lacrimal tube may be left in place for one month or longer, and sometimes for two months or longer. As a method for enabling continuous release for a long period of time, the mass of the anti-inflammatory agent or epithelial cell growth promoting agent is kept small (e.g., 50% by mass or less with respect to the resin), and the placement location is inside the tube (e.g., , a first coating region R1), and a method of adjusting the molecular weight of the biodegradable plastic, the copolymer composition ratio, etc. when controlling the release characteristics by utilizing the decomposition characteristics of the biodegradable plastic. .

Apart from the embodiment shown in FIG. 3, the tubular portion 5 of the tube of the present invention may be configured in a shape as shown in FIG. 4 or FIG. 4 and 5 are enlarged cross-sectional views of FIG. 1A for an embodiment different from FIG.

In the embodiment shown in FIG. 4 , a communication hole 10 communicating with the hollow portion of the cylindrical portion 5 in which the bougie hole is formed is provided on the opposite side of the bougie insertion direction D in the cylindrical portion 5 with respect to the bougie hole 7 . is provided. As a result, when tears flow from the communication hole 10 into the hollow portion, they come into contact with the anti-inflammatory agent or epithelial cell growth promoting agent placed inside the tube, so that a high effect of suppressing reocclusion can be obtained. Therefore, it is preferable to provide the communication hole 10 in the tubular portion 5 . The shape of the communication hole 10 is not particularly limited, and may be circular, for example.

In the embodiment shown in FIG. 5, a flow regulating valve 11 is provided in a hollow portion between the communication hole 10 and the bougie hole 7 to control the amount of tears flowing from the communication hole 10 toward the bougie hole. This makes it possible to obtain a higher sustained release property.

In the embodiment shown in FIG. 1, the lacrimal duct tube is composed of a pair of tubes, but it may not be composed of a pair, and for example, the cylindrical portion 5 may be composed of only one.

A hydrophilic coating may be provided on the outside of the lacrimal tube to enhance the insertion of the lacrimal tube into the lacrimal duct. In such a lacrimal duct tube, the coating exhibits lubricity when in contact with tears, blood, etc., and reduces resistance during insertion. The type of hydrophilic coating is not particularly limited, and hydrophilic polymers such as poly(2-hydroxyethyl methacrylate), polyacrylamide, polyvinylpyrrolidone, polyethylene glycol, or blends thereof are preferably used. However, when placing an anti-inflammatory drug or epithelial cell growth promoting agent on the outside of the tube, placing a hydrophilic coating on top of it may reduce the sustained release of the anti-inflammatory drug or epithelial cell growth promoting agent. Therefore, in this case, it is preferable not to provide a hydrophilic coating.

<Animal test>
New Zealand White rabbits (N=4) were used to assess the extent of the rate of injury lacrimal healing by rebamipide-placed lacrimal tube surfaces. As the operation, first, the lacrimal tubes of Example 1, Example 2, and Comparative Example 1 below were placed in the rabbit puncta (right and left lower puncta), and after a predetermined period of time (0 days (immediately after), 2 days, 6 8 days later), the lacrimal tube was removed, and the inside of the lacrimal duct was observed with a lacrimal endoscope to evaluate the extent of areas where epithelial cells had not regenerated. The predetermined period was set after confirming that wound healing in rabbits was almost completed by 8 days in a preliminary experiment (the wound healing rate in rodents is said to be several times that in humans).

Concerning the pretreatment of the rabbit, specifically, the rabbit was first fixed in a fixation device, anesthetized by inhalation, and then an eye drop anesthetic, an antibacterial agent, and an anti-inflammatory agent were applied to the eye. Thereafter, the inside of the lacrimal canaliculus was evenly rubbed with a 23G injection needle with a bent tip, and then toluidine blue was injected into the lacrimal canaliculus. After the injection, the tear was washed with physiological saline, and a lacrimal duct endoscope (Φ0.90 mm, manufactured by FT) was used to confirm that the damaged part was stained with toluidine blue and was present throughout. If the damage area was narrow, a scratching operation was added.

Lacrimal duct tubes of Example 1, Example 2, and Comparative Example 1 were prepared by the following procedure.

(Example 1)
As the lacrimal tube, a lacrimal tube consisting of a cylindrical portion having a 10 mm long bougie hole and a suture fixing portion for fixing the cylindrical portion is used. The one with the configuration shown in is used. Rebamipide and a biodegradable plastic (PLGA (copolymer of lactic acid and glycolic acid (20:80))) were mixed with N, Dissolved in N-dimethylformamide, coated and dried on the first coating region R1 in FIG. No. 1 lacrimal tube was made.

(Example 2)
A lacrimal tube of Example 2 was produced in the same manner as in Example 1, except that the tubular portion was configured so as not to have a bougie hole and the coating site was changed to the outside of the lacrimal tube.

(Comparative example 1)
A lacrimal tube of Comparative Example 1 was prepared in the same manner as in Example 1, except that rebamipide and biodegradable plastic were not coated.

(punctal placement)
Lacrimal punctal placement was performed on the lacrimal tubes of Examples 1 and 2 and Comparative Example 1 described above. Specifically, first, the lacrimal punctum was appropriately dilated with a dilating needle, and the lacrimal tube was inserted through the lacrimal punctum until the main body was completely inserted. After insertion, the suture-fixed part and the rabbit eyelid were fixed with sutures. In addition, antibacterial agents and anti-inflammatory agents were instilled after the operation.

(observation)
The lacrimal ducts of the above rabbits were observed immediately after placement (day 0), 2 days, 6 days, and 8 days after placement. A rabbit without an indwelling lacrimal tube was prepared as a control, and the inside of the lacrimal duct was also observed after 0, 2, 6 and 8 days. Specifically, first, the rabbit was fixed in a fixator and anesthetized by inhalation, and then an eye drop anesthetic, an antibacterial agent, and an anti-inflammatory agent were applied to the eye. At this time, punctum dilation was performed from the side of the indwelling lacrimal tube as needed. After that, toluidine blue was injected into the lacrimal canaliculus, and after the injection, the tears were washed with physiological saline. After that, the inside of the rabbit lacrimal duct was observed with a lacrimal endoscope to evaluate the extent of residual damage.

Fig. 2 shows an observed image of the inside of the lacrimal duct when the tube of Comparative Example 1 is placed in the left lacrimal duct of a certain rabbit, and an observed image of the inside of the lacrimal duct when the tube of Example 2 is placed in the right lacrimal duct of the same rabbit. 6. Further, an observation image of the inside of the lacrimal duct when the tube of Comparative Example 1 was placed in the left lacrimal duct of a certain rabbit, and an observation image of the inside of the lacrimal duct when the tube of Example 1 was placed in the right lacrimal duct of the same rabbit. is shown in FIG.

To evaluate the residual damage range, read the observed image using Adobe's Photoshop CS5 software, select the blue portion stained with toluidine blue with the selection tool, measure the area of that portion with the analysis tool, and occupy the whole This was done by quantifying the percentage of that area as the extent of residual damage (0% healed completely). The results are shown in Table 1 below. Analytical images obtained by performing the above quantification in FIGS. 6 and 7 are shown in FIGS. 8 and 9, respectively. In addition, in FIGS. 8 and 9, the blue portion dyed with toluidine blue is displayed in black.

As can be seen from the results shown in Table 1 and FIGS. 6 to 9, Examples 1 and 2 coated with rebamipide healed faster than Comparative Example 1 and the control. This suggests that placing rebamipide in the lacrimal tube can provide a therapeutic effect on the lacrimal duct and suppress reocclusion.

<Sustained release test>
The lacrimal tubes of Examples 3 to 5 were prepared, and the amount of residual coating (biodegradable plastic + rebamipide) was measured.

(Example 3)
A lacrimal duct tube of Example 3 was produced in the same manner as in Example 1 except that the mass of rebamipide was adjusted to 20% by mass with respect to the mass of the biodegradable plastic.

(Example 4)
A lacrimal duct tube of Example 4 was produced in the same manner as in Example 1, except that the mass of rebamipide was changed to 33% by mass with respect to the mass of the biodegradable plastic.

(Example 5)
A lacrimal duct tube of Example 5 was produced in the same manner as in Example 1, except that the mass of rebamipide was 10% by mass with respect to the mass of the biodegradable plastic.

(Confirmation operation of sustained release)
The lacrimal tubes of Examples 3 to 5 were suspended in physiological saline, and the amount of residual coating was measured over time. A precision balance was used to measure the amount of residual coating. Since the biodegradable plastic and rebamipide are insoluble in saline, the residual coating maintains its original weight ratio. The results are shown in FIG. As shown in FIG. 10, it was found that the larger the mass of rebamipide with respect to the biodegradable plastic, the more rapidly it was released, and the smaller the mass, the higher the sustained release.

1 Lacrimal duct tube 2a First bougie 2b Second bougie 3 Middle point 4 Central portion 5 Tubular portion 5a First tubular portion 5b Second tubular portion 6 First end 7 Bougie hole 7a First bougie hole 7b Second bougie Hole 8 Second end 9a Mark 9b Mark 10 Communication hole 11 Flow control valve 21 Upper punctum 22 Lower punctum 23 Upper canaliculus 24 Lower canaliculus 25 Common canaliculus 26 Lacrimal sac 27 Nasolacrimal duct 28 Lower nasal meatus R1 First Coating area R2 Second coating area R3 Third coating area D Bougie insertion direction

Claims (7)

A lacrimal tube comprising a pair of tubular parts and a central part connecting them,
an anti-inflammatory agent or epithelial cell growth promoting agent disposed on a first coating area on the inner surface of the lacrimal tube ;
The cylindrical portion includes a bougie hole,
The first coating region is a region opposite to the bougie insertion direction with respect to the bougie hole, and is a region located on the bougie insertion direction side of the connecting portion between the central portion and the cylindrical portion. . 2. The lacrimal tube of Claim 1, wherein said anti-inflammatory agent or said epithelial cell growth promoting agent is rebamipide or an analogue thereof. The anti-inflammatory agent or epithelial cell growth-promoting agent is dispersed in a biodegradable polymer, and the mass of the anti-inflammatory agent or epithelial cell growth-promoting agent is greater than 0% by mass relative to the biodegradable polymer . The lacrimal tube according to claim 1 or 2 , which is 60% by mass or less. The anti-inflammatory agent or epithelial cell growth-promoting agent is dispersed in a biodegradable polymer, and the mass of the anti-inflammatory agent or epithelial cell growth-promoting agent is greater than 0% by mass relative to the biodegradable polymer . The lacrimal tube according to claim 1 or 2 , which is 35% by mass or less. The anti-inflammatory agent or epithelial cell growth-promoting agent is dispersed in a biodegradable polymer, and the mass of the anti-inflammatory agent or epithelial cell growth-promoting agent is greater than 0% by mass relative to the biodegradable polymer. The lacrimal tube according to claim 1 or 2, which is 20% by mass or less. The anti-inflammatory agent or epithelial cell growth-promoting agent is dispersed in a biodegradable polymer, and the mass of the anti-inflammatory agent or epithelial cell growth-promoting agent is greater than 0% by mass relative to the biodegradable polymer. The lacrimal tube according to claim 1 or 2, which is 10% by mass or less. The lacrimal tube according to any one of claims 1 to 6 , wherein the anti-inflammatory agent or the epithelial cell growth promoting agent is configured to be continuously released for 30 days or more.

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