JPH0592016A - Rod for damming up outflow of tears - Google Patents

Abstract

PURPOSE:To obtain the rod for damming up the tears which is less fluctuated in a dissolution speed by using a copolymer of one or >=2 kinds of p-dioxanon and lactide. CONSTITUTION:The lactide is more specifically exemplified by cyclic cliester consisting of two molecules of alpha oxyacid, such as glycolic acid, lactic acid and alpha hydroxy lactic acid, and the generally used lactide is lactide consisting of a glycolic acid unit and lactide consisting of a lactic acid unit. The copolymer is obtd. by successively polymerizing a p-dioxane monomer and a lactide monomer in the presence of a catalyst, such as stannous octanoate, etc. The resulted copolymer is melt spun by using a plunger extruder, etc., and is cooled to solidify; thereafter, the extruded polymer is cut to a desired length, by which the rod for preventing the outflow of the tears is obtd. A dry eye symptom is decreased by using such rod for preventing the outflow of the tears. Since the dissolution speed is uniform, the management of an insertion schedule is easy and in addition, the unstability as to bioaffinity is lessened.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a tear flow stop rod. More specifically, the present invention relates to a tear fluid flow stop rod made of a soluble copolymer.

[0002]

2. Description of the Related Art The role of tears is important in human daily life. It is well known that it prevents the eyes from drying out, wash away foreign substances such as dust that got into the eyes, and also has a bactericidal action. Is a fact of.

Further, as a recent tendency, it is said that the number of dry eye (lacrimal fluid deficiency) patients is increasing among computer workers who watch a television screen for a long time. After the tears secreted by the tears wet the surface of the cornea, they flow to the nose side and enter the punctum, and then flow out to the lower nasal passage through the lacrimal canaliculus, the lacrimal canal, and the nasolacrimal duct. The area from this punctum to the lower nasal passage is called the lacrimal passage.

A method for reducing the amount of lacrimal fluid flowing out of the lacrimal passage has been proposed for dry eye patients as described above. For example, there are punctal plugs as described in US Pat. No. 3,949,750. This method is to stop the flow of tear fluid by plugging the entrance of the lacrimal passage. According to this method, since the upper part of the plug is exposed from the punctum, this part may touch the cornea, may cause scratches on the cornea, and has a drawback that it is easily dislocated from the punctum.

Further, Japanese Patent Laid-Open No. 61-115559 proposes to insert a rod of cut gut into the lacrimal passage. Since cut gut or collagen dissolves within 10 to 15 days after being inserted into the lacrimal duct, it is a method that does not cause trouble due to long-term retention such as when a plastic rod is inserted, but collagen is a natural material. Since the animal intestine and the like are used, there is a drawback that the texture and the dissolution rate vary greatly due to the nature of the tissue used and natural biological changes. In addition, it is a well-known fact that collagen easily causes an anti-source antibody reaction and has a problem of biocompatibility.

[0006]

DISCLOSURE OF THE INVENTION The present invention provides a rod for preventing tear flow, which has uniform solubility and has a small variation in the dissolution rate without causing the secondary adverse effects that occur during use as described above. The purpose is to provide.

[0007]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies on various materials in order to solve such problems, and as a result, found that a copolymer of p-dioxanone and one or more kinds of lactide was The present invention has been found to dissolve in the lacrimal passage and has led to the present invention. A copolymer of p-dioxanone and one or more lactides is a relatively well-known material for sutures, and is known to dissolve in living tissues. However, it was a surprising fact that it dissolves in the lacrimal passage, which is not necessarily in living tissue.

[0008] That is, the present invention is a tear flow stop rod comprising a copolymer of p-dioxanone and one or more lactides. The use of a rod for preventing tear flow outflow is carried out by inserting it from the punctum, and its size is usually selected from a range of 0.5 to 5 mm in length and 0.1 to 1.5 mm in diameter, and a length of 1 0.0-3.0 mm, diameter 0.
2 to 0.8 mm is the most common. However, this should be selected according to the size of the punctum of each individual, and the optimum length and radius of the rod may be determined according to the person who uses it.

Further, the lactide referred to in the present invention means the one represented by the following chemical formula 1.

[0010]

[Chemical 1]

Specifically, glycolic acid, lactic acid, α-hydroxybutyric acid, α-hydroxyisobutyric acid, α-hydroxyvaleric acid, α-hydroxyisovaleric acid, α-hydroxycaproic acid, α-hydroxy-α-ethyl. Butyric acid, α-hydroxyisocaproic acid, α-hydroxy-β-methylvaleric acid, α-hydroxyheptanoic acid, α-hydroxyoctanoic acid, α-hydroxydecanoic acid, α-hydroxymyristic acid, α-hydroxystearic acid, α Examples thereof include cyclic diesters composed of two molecules of α-oxy acid such as hydroxylignoceric acid.

The most commonly used of these is lactide consisting of glycolic acid units, ie lactide consisting of glycolide and lactic acid units. In the copolymer used in the present invention, the compounding ratio of p-dioxanone and lactide can be arbitrarily selected, but is preferably in the range of 99 to 1 mol% p-dioxanone and 1 to 99 mol% lactide. However, when a lactide other than glycolide is used, its content is preferably 50 mol% or less, more preferably 35 mol% or less. If the blending ratio of lactide other than glycolide is large, the dissolution time when used as a tear flow prevention rod will be longer than necessary, which may cause trouble due to long-term retention.

Further, the intrinsic viscosity (IV) value measured at a copolymer concentration of 0.1 g / dl in hexafluoroisopropyl alcohol (25 ° C.) is 0.4 to 3.5.
Is preferable, and more preferably 0.5-2.
7 is a copolymer. If the intrinsic viscosity is less than 0.4, it will be difficult to perform cutting after cooling during melt molding, and if it exceeds 3.5, the melt viscosity will be large and the melt molding will be difficult.

The copolymer used in the present invention comprises a p-dioxanone monomer and a lactide monomer in the presence of a catalyst such as stannous octoate as disclosed in, for example, JP-A-62-164718. It can be obtained by sequentially polymerizing. The copolymer thus obtained,
A rod for preventing tear flow can be obtained by melt spinning using a plunger extruder, cooling and solidifying, and then cutting this to a desired length.

Since the tear flow preventing rod thus obtained is not made of a natural product such as collagen, it has disadvantages caused by biological influences in the natural world.
For example, the nonuniformity of the solubility has been greatly improved. Needless to say, for the purpose of stabilizing the above-mentioned copolymer, for example, a tear flow preventing rod made of a compound in which an end group is esterified is also included in the present invention.

Further, for the purpose of improving the handling property during insertion, it is also possible to coat with various surfactants, for example, a coating agent such as calcium stearate for use. It is also possible to add a stabilizer such as triphenyl phosphite, dialkylphenol sulfide and aromatic disulfide phenol.

If desired, it may be colored with a suitable coloring agent.

[0018]

The present invention will be described in more detail with reference to the following examples.

[0019]

Example 1 According to the method described in JP-A No. 62-164718, a solution of 0.1% in hexafluoroisopropyl alcohol was used.
P-dioxanone / L (-) of copolymer having an intrinsic viscosity of 2.5 measured using a copolymer solution of 1 g / dl (25 ° C)
A copolymer of p-dioxanone and L (-) lactide having a lactide molar ratio of 82.5 / 17.5 was obtained. The L (-) lactide used here was composed of lactic acid units. Insert this copolymer into the plunger extruder,
What was melt-prevented at 200 ° C. and cooled and solidified in water was cut by a cutter to obtain a rod for preventing tear flow outflow having a diameter of 0.3 mm and a length of 2 mm.

[0020]

[Example 2] According to the method described in JP-A-62-164726, a solution of 0.1% in hexafluoroisopropyl alcohol was prepared.
A copolymer of p-dioxanone and glycolide having an intrinsic viscosity of 1.63 measured using a 1 g / dl copolymer solution (25 ° C.) and a copolymer p-dioxanone / glycolide molar ratio of 94/6 was prepared. Obtained.

This copolymer was prepared in the same manner as in Example 1,
Thus, a rod for stopping tear flow was provided with a diameter of 0.3 mm and a length of 2 mm.

[0022]

Example 3 Intrinsic viscosity 1.78 measured by the method described in Example 2 using a copolymer solution of 0.1 g / dl in hexafluoroisopropyl alcohol (25 ° C.), p-dioxanone of the copolymer / Molar ratio of glycolide 41.2 /
A copolymer of p-dioxanone and glycolide of 58.8 was obtained. From this copolymer, a tear flow preventing rod having a diameter of 0.3 mm and a length of 2 mm was obtained in the same manner as in Example 1.

1 mm of the rods obtained in Examples 1, 2 and 3
Cut into long pieces, each weighing 3.2 to 3.5 kg
A total of 6 white rabbits were inserted from the left and right tears.
After 3 months, the lacrimal passage was incised, and the rod had dissolved and disappeared.

[0024]

EFFECTS OF THE INVENTION By using the rod for preventing tear outflow according to the present invention, dry eye symptoms are alleviated and the dissolution rate is uniform, so that the insertion schedule can be easily controlled, and in addition, there is concern about biocompatibility. Will be reduced.

Claims (1)

[Claims] 1. A rod for preventing tear flow out, comprising a copolymer of p-dioxanone and one or more lactides.