HK1152467B - Method of producing medical instrument - Google Patents

Description

Method for manufacturing medical tool

Technical Field

The present invention relates to a method for manufacturing a medical tool having a coating layer provided on a surface thereof. The invention further relates to an intraocular lens insertion tool provided with a coating.

Background

When contact lenses and intraocular lenses, insertion tools for intraocular lenses, endoscopes, catheters, tubes, and various similar grades of medical tools are used, the surface of the medical tool frequently comes into direct contact with biological tissue, sliding against each other. However, since most medical tools are made of materials such as metal or resin, lubricity is low and hydrophilicity is lacking during contact with biological tissue, thereby causing a risk of problems such as deterioration of the medical tool or inflammation caused by friction.

For this reason, as disclosed in patent documents 1 to 4, techniques have been conceived in the past: the lubricity and hydrophilicity of the surface of a medical tool such as a catheter or intraocular lens insertion tool is improved by coating the surface of the medical tool with any of various grades of hydrophilic polymers.

However, it is not easy to form a stable hydrophilic polymer coating on the surface of a hydrophobic substrate such as metal or polypropylene, and it is a frequent problem that satisfactory coating strength, durability or lubricity cannot be achieved.

Specifically, according to the coating techniques disclosed in patent document 1 and patent document 2, the coating layer formed on the surface of the medical tool is made of a hydrophilic polymer, and thus there is a problem that if the coating layer comes into contact with water, the polymer is eluted into the solution so that the coating effect is lost. Other problems include poor adhesion between the coating and the surface being coated resulting in a failure to produce a uniform coating and premature peeling of the coating as a whole.

The technique disclosed in patent document 3 attempts to form a main layer of a polymer such as polyurethane on the surface of a medical tool (stent in this example); the heparin molecules bound thereto are then used to create a polymer sublayer. However, since this process requires the formation of two coating layers, there arises a problem that labor and cost associated with the coating process are increased.

Meanwhile, an intraocular lens insertion tool, which is another type of medical tool, is designed to push out a compactly folded intraocular lens into an eye through an insertion tube in the shape of a tiny tube so as to insert the intraocular lens into the eye through a tiny incision formed in eye tissue such as the cornea. However, even if an ophthalmic viscoelastic material is used as a lubricant, a problem is encountered during the push-out operation in that the intraocular lens is not smoothly pushed out due to an improper level of lubrication or lack of lubrication between the intraocular lens and the inner surface of the insertion tube made of a hydrophobic material.

For this reason, it is conceived to improve the lubricity of the intraocular lens by forming a coating layer inside the intraocular lens insertion tool, as disclosed in patent document 4. However, since a hydrophilic polymer such as cellulose soluble in water is employed as a component of the coating layer, problems similar to those in the techniques disclosed in patent documents 1 and 2 are encountered, that is, weak adhesion and adhesion between the coating layer and the surface of the hydrophobic insertion tool cause a tendency of the coating layer to delaminate. Another problem is that when the coating is in direct contact with water during use, the water-soluble coating components elute into solution quickly so that surface lubricity is not maintained. Further, since the coating liquid is a water-based solution, it tends to aggregate due to high surface energy, making it difficult to form a uniform thin coating layer. Therefore, the intraocular lens insertion tool does not have sufficient lubricity or hydrophilicity necessary for pushing out the lens.

Patent document 1: JP-T2006-510756

Patent document 2: JP-T2005-537097

Patent document 3: JP-T2006-500987

Patent document 4: JP-T10-512172

Disclosure of Invention

Problems to be solved by the invention

In view of the foregoing, accordingly, an object of the present invention, in its aspect relating to a method for manufacturing a medical tool, is to provide a method for manufacturing a medical tool, whereby exceptionally good hydrophilicity and lubricity can be imparted to the surface of the medical tool by forming a very durable coating layer having high hydrophilicity and lubricity by means of a simple method. In another aspect relating to an intraocular lens insertion tool, the present invention provides an intraocular lens insertion tool adapted to be smoothly inserted into an intraocular lens by means of forming a coating layer having exceptionally good hydrophilicity and lubricity on the surface of an insertion portion.

Means for solving the problems

The following discloses aspects of the present invention relating to a method for manufacturing a medical tool and aspects relating to an intraocular lens insertion tool. The elements employed in the following modes of the invention may be employed in any possible optional combination. It is to be understood that the modes and technical features of the present invention are not limited to those disclosed herein, but may be recognized based on the teachings disclosed throughout the detailed description and the accompanying drawings, or may be recognized by those skilled in the art based on the inventive concept provided by the present disclosure.

First, the invention related to a method for manufacturing a medical tool provides a method for manufacturing a medical tool adapted to impart hydrophilicity and lubricity to a surface of the medical tool by forming a coating layer on the surface of the medical tool, the method comprising: a coating solution preparation step in which at least (a) a water-insoluble polymer having a carboxyl group and (b) a polyfunctional active compound are dissolved in an organic solvent to obtain a coating solution; a coating step in which the coating solution is applied to the surface of the medical tool to form a coating layer; a crosslinking step, wherein the coating undergoes crosslinking; and a chemical reaction step in which a chemical reaction treatment is performed to cause hydrophilization of the crosslinked coating layer.

In the method for manufacturing a medical instrument according to the present invention, the water-insoluble polymer having a carboxyl group is easily dissolved in an organic solvent for the coating solution, and a uniform coating layer can be advantageously formed on the surface of the medical instrument. The term "medical tool" herein is intended to include catheters, endoscopes, laryngoscopes, tubes, extracorporeal blood circuit tubes, contact lenses, intraocular lens insertion tools, and the like. The surface of the medical tool herein refers to a concept that: it includes component surfaces of various medical tools, such as inner surfaces, outer surfaces, and tubular inner circumferential surfaces, which require such surface lubricity between the medical tool and biological tissue during medical procedures.

The water-insoluble polymer molecules are cross-linked with each other due to the presence of the polyfunctional reactive compound in the coating solution, thereby preventing the decomposed polymer molecules from being dissociated even if some adhesion of the long-chain water-insoluble polymer is deteriorated for some reason, thereby remarkably improving the strength and durability of the coating layer.

In the present invention, the coating layer can be easily rendered hydrophilic by a simple means of subjecting the coating layer containing the water-insoluble polymer having a carboxyl group to a chemical reaction treatment to cause hydrophilization. Furthermore, by crosslinking together the water-insoluble polymers by means of the polyfunctional reactive compounds, the elution of the hydrophilized polymers from the coating can be reduced even if the coating is brought into contact with water. Furthermore, since only the outer side surface of the coating layer becomes hydrophilized and the contact surface with the surface of the medical implement does not become hydrophilized, the adhesion, adhesion and strength of the coating layer are not impaired, and the coating layer resists delamination. As a result, a hydrophilic coating having exceptionally good durability can be easily achieved by simple processing.

In the present invention, the water-insoluble polymer having a carboxyl group is preferably selected from the group consisting of hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, cellulose acetate phthalate and a mixture thereof.

These substances all have the property of becoming water-soluble by pH-dependent dissociation of carboxyl groups in the molecule when the pH of the solution rises from acidic to neutral or alkaline, and are therefore generally referred to as enterocellulose. In the present invention, the formation of the coating is advantageously carried out utilizing this characteristic. Specifically, in the coating solution preparation step and the coating step, since these substances are soluble in water, mixing with an organic solvent such as acetone and coating on the surface of the medical instrument can take place under favorable conditions; and these substances can be easily hydrophilized by a subsequent chemical reaction treatment, thereby providing hydrophilicity to the coating layer by simple means and imparting exceptionally good lubricity and hydrophilicity to the surface of the medical instrument.

In the present invention, the coating solution preferably includes 0.1 to 10 parts by weight of the water-insoluble polymer having a carboxyl group, 0.01 to 5 parts by weight of the polyfunctional active compound, and 1 to 100 parts by weight of the organic solvent. According to this formulation, the formation of the coating layer can be carried out more advantageously.

In the present invention, the polyfunctional reactive compound is selected from the group consisting of isocyanates, epoxides, acid chlorides, acid anhydrides, triazines, reactive esters, and mixtures thereof.

By using any of these as the polyfunctional reactive compound, better crosslinking between polymer chains insoluble in water can be caused and the durability of the coating can be improved. In particular, by crosslinking of the polymer molecules through the medium of the polyfunctional active compound, elution of the polymer molecules can be advantageously limited even after the water-insoluble polymer having carboxyl groups has been rendered hydrophilic by a chemical reaction treatment.

In the present invention, the coating solution preferably contains a surfactant.

The hydrophilicity of the coating layer can be further improved by adding a surfactant to the coating solution. The addition of the surfactant enables the chemical reaction treatment to take place under more favorable conditions. A leveling (uniform spreading of the film) effect is also produced during application of the coating solution to the medical tool. The surfactant may be added to the substrate of the medical tool in advance.

In the present invention, during the aforementioned coating step, after the coating solution is coated on the surface of the medical instrument, it is preferable to suck the coating solution or rotate the medical instrument to subject the coating solution to a centrifugal force in order to spread the coating solution in a layer on the surface of the medical instrument and to remove an excess of the coating solution from the surface of the medical instrument.

This treatment provides a smoother coating of uniform thickness, further improving lubricity of the medical tool surface.

In the present invention, the neutralization method is preferably employed as the chemical reaction treatment in the chemical reaction step.

Thus, the water-insoluble polymer can be easily rendered hydrophilic by a very simple measure of neutralizing the carboxyl group of the water-insoluble polymer.

Meanwhile, the invention related to an intraocular lens insertion tool provides an intraocular lens insertion tool which includes a substantially tubular tool body accommodating an intraocular lens therein, and is adapted to move the intraocular lens axially forward by an ejecting member (plunging member) inserted into the tool body from the axial rearward direction while causing the lens to deform to a smaller size and eject the lens into the eye through an insertion tube portion provided at the axial front end portion of the tool body; wherein the surface of the inside of the insertion tube part is imparted with hydrophilicity and lubricity by a coating layer formed thereon; and the coating is comprised of a crosslinked chemically treated film formed by the steps of: a coating solution preparation step in which a water-insoluble polymer having at least a carboxyl group and a polyfunctional active compound are dissolved in an organic solvent to obtain a coating solution; a coating step in which the coating solution is applied to the surface of the medical tool to form a coating layer; a crosslinking step, wherein the coating undergoes crosslinking; and a chemical reaction step in which a chemical reaction treatment is performed to cause hydrophilization of the crosslinked coating layer.

According to the invention relating to the intraocular lens insertion tool, a coating layer equivalent to the coating layer formed according to the invention relating to the aforementioned method of manufacturing the medical tool can be formed on the inner surface of the intraocular lens insertion tube portion. Specifically, a coating layer imparted with exceptionally good hydrophilicity and lubricity and having exceptionally good durability can be formed in the intraocular lens insertion tube portion, thereby preventing sticking between the intraocular lens and the insertion tool and improper deformation of the intraocular lens during insertion of the intraocular lens, so that the intraocular lens can be stably pushed out in a smooth manner.

Drawings

Fig. 1 is a perspective view showing an intraocular lens insertion tool according to an embodiment of the present invention;

fig. 2 is a partially enlarged view of the insertion tool shown in fig. 1.

Description of the reference numerals

10: an insertion tool; 12: a tool body; 14: a plunger; 20: a platform; 26: an intraocular lens;

34: nozzle part

Detailed Description

The following first describes embodiments of the invention relating to a method of manufacturing a medical implement in order to provide a more specific understanding of the invention relating to a method of manufacturing a medical implement.

Examples of medical tools in which the invention may be implemented in manufacture include various known grades of medical tools made of metal or resin, such as contact lenses, intraocular lens insertion tools, catheters, stents, and the like. Intraocular lenses refer to lenses designed for insertion into the eye to replace the crystalline lens in order to treat diseases such as cataracts. As will be described later, the present invention is particularly suitable for use in manufacturing an intraocular lens insertion tool.

According to the present invention, medical tools having improved hydrophilicity and lubricity can be produced by forming a coating layer on the surface of these medical tools. Next, a specific method for forming a coating layer on the surface of the medical tool is described.

First, the coating solution in the present invention includes a water-insoluble polymer having a carboxyl group and a polyfunctional reactive compound. Any of various known water-insoluble polymers having a carboxyl group may be used as the water-insoluble polymer having a carboxyl group as long as the object of the present invention can be achieved. In preferred practice, at least one of hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate is employed. Other specific examples are copolymers of (meth) acrylic acid with other radically polymerizable monomers, such as acrylic acid-octyl acrylate copolymer or PEMULEN TR-1 (trademark) and EMULEN TR-2 (trademark) manufactured by Nikko Chemicals co., Ltd.), but are not limited thereto as long as the compound is a water-insoluble (meth) acrylic acid copolymer. Further examples are phthalic acid containing (meth) acrylates, such as acryloyloxyethylphthalate monoesters, either alone or in copolymer with another copolymerizable monomer. Another example is polyamic acid, i.e. a polymer of tetracarboxylic dianhydride and a diamino compound, which is also a precursor of polyimide. Specific examples are aromatic polyimides synthesized from pyromellitic dianhydride and 4, 4 ' -diaminodiphenyl ether, and aromatic polyimides synthesized from 3, 3 ', 4, 4 ' -biphenyltetracarboxylic dianhydride and p-phenylenediamine, and the like. Any of various water-insoluble polymers having a carboxyl group may be used alone, or several different water-insoluble polymers having a carboxyl group may be used in combination as the water-insoluble polymer having a carboxyl group in the present invention.

Hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose succinate acetate or cellulose acetate phthalate, which are used as the water-insoluble polymer having a carboxyl group in the present invention, are all types of cellulose belonging to a group called enterocellulose. Enteric cellulose is the name given to cellulose that exhibits particular properties, whereby when taken orally, the compound dissolves not in the stomach, but in the intestine. In other words, these compounds have hydrophobicity in a low pH acidic environment such as gastric acid, while they become hydrophilic by dissociation of hydrogen atoms of carboxyl groups in the molecules in a high pH, i.e., highly basic environment.

According to the present invention, by selecting such an enteric cellulose particularly suitable for use in a coating solution, a coating layer can be formed utilizing the characteristics of a compound which is easily dissolved in a solvent in an untreated state in a coating solution preparation step and a coating step which will be described later; and then the coating can be easily rendered hydrophilic by neutralization hydrophilization in a chemical reaction step.

According to the invention, the coating solution contains a polyfunctional reactive compound. Specific examples of polyfunctional reactive compounds which can be advantageously employed are isocyanates, epoxides, acid chlorides, acid anhydrides, triazines, reactive esters and other known substances which are highly reactive by containing several functional groups. Specific examples of acid chlorides are adipic acid dichloride and the like. Examples of anhydrides are maleic anhydride, citraconic anhydride, itaconic anhydride and other similar unsaturated carboxylic anhydrides, as well as tetracarboxylic dianhydride and VEMA manufactured by Daicel chemical industries. Any of these various polyfunctional reactive compounds may be used alone, or a mixture of several different polyfunctional reactive compounds in combination may be used as the polyfunctional reactive compound in the present invention.

The coating solution in the present invention preferably includes a bound surfactant in addition to the above-mentioned water-insoluble polymer having a carboxyl group and the polyfunctional active compound. Any of various known substances having a surface-active action may be used as the surfactant; however, compounds having functional groups reactive with the polyfunctional reactive compounds are preferred. Examples include: alkyl glycerol ethers such as glycerol monocetyl ether and glycerol monooleyl ether; glycerin fatty acid esters such as glycerin monostearate and glycerin myristate; polyoxyethylene glycerin fatty acid esters such as polyoxyethylene (5) glyceryl monostearate, polyoxyethylene (15) glyceryl monolaurate and polyoxyethylene (5) glyceryl monooleate; sorbitan fatty acid esters such as sorbitan monolaurate and sorbitan monopalmitate; polyoxyethylene sorbitan fatty acid esters such as sorbitan polyoxyethylene (20) ether monolaurate (tween 20), sorbitan polyoxyethylene (20) ether monopalmitate (tween 40) and sorbitan polyoxyethylene (20) ether monostearate (tween 60); polyoxyethylene hydrogenated castor oils such as polyoxyethylene (10) hydrogenated castor oil and polyoxyethylene (20) hydrogenated castor oil; polyoxyethylene alkyl ethers such as dodecylpolyoxyethylene (9) ether, dodecylpolyoxyethylene (25) ether, hexadecylpolyoxyethylene (10) ether and octadecylpolyoxyethylene (20) ether; polyoxyethylene polyoxypropylene alkyl ethers such as cetyl polyoxyethylene (10) polyoxypropylene (4) ether and decyl tetradecylpolyoxyethylene (12) polyoxypropylene (6) ether; and polyethylene glycol fatty acid esters such as polyethylene glycol monolaurate (10EO) and polyethylene glycol monostearate (10 EO). During the production of a medical tool of a resin base material such as polypropylene, a surfactant may be added to the base material in advance.

According to the present invention, in the coating solution preparing step, the water-insoluble polymer having a carboxyl group, the polyfunctional active compound, and the surfactant are mixed in the organic solvent to prepare the coating solution. Organic solvents that can be used for the purpose of the present invention include various known organic solvents such as acetone, toluene, xylene, methyl ethyl ketone, ethoxyethyl acetate, tetrahydrofuran, dichloromethane, chloroform, ethyl acetate, and acetonitrile; here, it is particularly preferable to select an organic solvent: which readily dissolves water-insoluble polymers having carboxyl groups, has a suitable level of volatility and is furthermore inert towards polyfunctional active compounds. For example, in the case of using hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate or cellulose acetate phthalate as the water-insoluble polymer having a carboxyl group, acetone is preferably selected.

The specific components and mixture ratio of the coating solution used in the present embodiment can be freely selected within the range to achieve the object of the present invention. In preferred practice, the solution contains: a water-insoluble polymer having a carboxyl group at a level of 0.1 to 10 parts by weight, preferably 0.5 to 5 parts by weight, and more preferably 1 to 2 parts by weight; a polyfunctional active compound at a level of 0.01 to 5 parts by weight, preferably 0.05 to 3 parts by weight, and more preferably 0.1 to 1 part by weight; a surfactant at a level of 0.01 to 5 parts by weight, preferably 0.05 to 1 part by weight; and an organic solvent at a level of 1 to 100 parts by weight, preferably 2 to 99 parts by weight, and more preferably 20 to 31 parts by weight.

Next, a coating step is performed in which the coating solution obtained in the above-described coating solution preparation step is applied to the surface of the medical tool in layers. Prior to the coating step, the surface of the medical tool may be subjected to a surface treatment step, such as plasma treatment, ultraviolet irradiation treatment, excimer laser treatment, or the like.

Next, a coating step is performed on the surface of the medical implement to apply a layer of the coating solution to the surface of the medical implement. The coating step of the present invention may employ known coating methods such as dipping, spraying, brushing or roll coating, but preferably employs methods such as the following.

First, a sufficient amount of freshly prepared coating solution is dropped onto the surface of the coated medical implement. Then, with the coating solution resting on the surface, the entire medical tool is fixed on a rotating platform and rotated. The generated centrifugal force acts on the coating solution to spread the coating solution outward from the center of rotation; in addition, excess coating solution in excess of the amount required to cover the surface being coated is removed from the medical tool surface by the action of centrifugal force. By adopting such a coating method, a coating layer having a smooth surface with a prescribed thickness can be easily formed on the surface of the medical tool with high accuracy. In addition to the method using a rotating centrifugal force, a method of sucking a coating solution to spread the coating solution while removing an excess solution may be employed as the coating method. Where centrifugal force is employed, spreading of the coating solution and removal of excess solution may be accomplished in a single rotation operation; or the operation may be performed in multiple platforms at the same or different rotational speeds. By multi-platform rotating operation, the articles can be subjected to centrifugal forces in different directions. A combination of the rotation method and the suction method may also be employed.

Next, in the crosslinking step according to the present invention, a crosslinking treatment is performed on the coating solution applied on the surface of the medical tool. The crosslinking treatment according to the present invention may be appropriately selected from various known treatments such as radiation irradiation, UV irradiation, heat treatment, or chemical treatment, depending on the type and combination of the water-insoluble polymer and the polyfunctional reactive compound in the coating layer. A single treatment, such as heat treatment, or a combination of several different treatments may be employed as the crosslinking treatment of the present invention. In the case of using isocyanate as the polyfunctional reactive compound in the present invention, it is preferable to use heat treatment for the crosslinking treatment. The preferred temperature range and treatment time in this case is 40 to 100 ℃ and 1 minute to 24 hours.

By performing such a crosslinking treatment, the crosslinking reaction is accelerated by the polyfunctional reactive compound to cause crosslinking of each polymer chain of the water-insoluble polymer having a carboxyl group, thereby bonding them together. So that the strength and durability of the coating are remarkably improved.

Once the crosslinking step has been completed, the coating is next subjected to a chemical reaction step in which a chemical reaction treatment is performed on the coating to impart hydrophilicity. Any of various chemical reaction treatments can be employed as the chemical reaction treatment in the present invention as long as the object of the present invention can be achieved, but a neutralization treatment (alkali treatment) is preferable. By subjecting the coating layer to such a neutralization treatment, the hydrogen atoms of the carboxyl groups of the water-insoluble polymer are dissociated or neutralized, with the result that the coating layer is provided with hydrophilicity. A specific example of the neutralization treatment is to immerse the surface of the coated medical tool in a 0.1-5% aqueous solution of sodium bicarbonate for 1 second to 120 minutes. The neutralizing agent may be selected from compounds such as potassium carbonate, potassium bicarbonate, potassium hydroxide, sodium carbonate, and other alkali or alkaline earth metal salts.

After the chemical reaction step, a cleaning step and a drying step are performed by a known method to complete the coating on the surface of the medical tool.

In this embodiment, the hydrophilic coating on the surface of the medical tool is completed by a simple measure of forming a coating of a water-insoluble polymer having a carboxyl group and then providing it with hydrophilicity by a neutralization treatment. In particular, it is not necessary to perform multi-layer coating with a polymer-based layer and a hydrophilic polymer layer to produce a hydrophilic coating layer, because high lubricity and excellent hydrophilic coating ability are provided by a single coating structure consisting of only a single layer. Therefore, a medical tool having exceptionally good hydrophilicity and lubricity can be obtained without increasing the number of manufacturing steps.

By crosslinking the coating solution by means of the polyfunctional reactive compound, elution of the coating components into the solution is prevented in the case of contact of the coating with the solution. So that the coating properties can be advantageously maintained.

The present invention relating to the manufacturing method of the medical tool is preferably realized in the manufacture of an intraocular lens insertion tool. Specifically, by forming a coating layer on the surface of an intraocular lens insertion tool according to the present invention, an intraocular lens insertion tool exhibiting excellent lubricity between the intraocular lens and the insertion tool during the ejection of the intraocular lens is easily provided.

Embodiments of the invention relating to an intraocular lens insertion tool are described in detail below with reference to the accompanying drawings.

First, an intraocular lens insertion tool 10 according to a first embodiment of the present invention is shown in fig. 1. The insertion tool 10 is composed of a generally tubular tool body 12, and a plunger 14 provided as an ejecting member passes through the inside of the tool body 12. Herein, "front" refers to an extending direction of the insertion tool 10 (a lower left direction in fig. 1), and "upper" refers to an upper direction in fig. 1. The "left-right direction" refers to the left-right direction in which the tool 10 is inserted in the rear view (in fig. 1, the lower-right direction represents the left and the upper-left direction represents the right). The insertion tool 10 of the present embodiment has been molded from a base material having polypropylene as a main component, to which glyceryl monostearate has been added in advance.

More specifically, the tool main body 12 has a substantially tubular main tube portion 16. The through hole 15 having a substantially elliptical cross section passes through the inside of the main pipe portion 16 in the axial direction.

A platform 20 is formed in front of the main tube portion 16 of the tool body 12. As shown in fig. 1, the groove 22 having a width dimension slightly larger than the diameter dimension of the main body 27 of the intraocular lens 26 extends through the platform 20 in the axial direction, and is opened upward so that the base face thereof functions as a seating face 30 for the intraocular lens 26.

As shown in fig. 1, the intraocular lens 26 accommodated in the insertion tool 10 of the present embodiment includes a main body 27 provided with an optical region, and a pair of holding portions 28, 28 that project circumferentially outward from the main body 27 and serve to position the main body 27 within the eye.

The intraocular lens 26 is disposed on the seating surface 30 through the opening 29. On one side (the right side in the present embodiment) of the opening 29, a cover portion 32 provided as a covering portion is formed integrally with the tool body 12, and after the intraocular lens 26 has been set at a prescribed location, the opening 29 is covered by the cover portion 32.

A nozzle unit 34 provided as an insertion tube unit is integrally formed at the axial front end of the tool body 12 in front of the platform 20. The nozzle portion 34 has a contour that tapers from a base end portion on the tool body 12 side toward a tip end in the projecting direction, and is formed with a through hole 36 that penetrates the entire length in the projecting direction.

As shown in fig. 2, the through hole 36 is connected to the stage 20 at a proximal end opening 38 thereof that opens toward the tool main body 12, so as to communicate with the stage 20. The cross section of the through hole 36 gradually becomes smaller from the base end opening 38 toward the leading end opening 40. In the widthwise central portion of the base surface of the nozzle unit 34, a protruding guide portion 42 of a linear shape protruding slightly upward and extending in the axial direction of the tool body 12 is formed.

Thus, the tool body 12 of the present embodiment is designed as a single component composed of the integrally formed main tube portion 16, the stage 20, the cap portion 32, and the nozzle portion 34. Since the tool main body 12 is a light-transmitting member, even in the case where the stage 20 is covered with the cover portion 32, the intraocular lens 26 contained in the tool main body 12 is visible through the cover portion 32.

In the present embodiment, the tool body 12 is made of polypropylene, but the material of the tool body 12 can be freely selected from various other materials such as resin or metal. The steps disclosed above in the embodiment of the invention relating to the manufacturing method of the medical tool are performed on the inner surface of the through hole 36 of the nozzle unit 34 of the tool main body 12 to form a coating layer thereon.

First, a coating solution for forming a coating layer is separately prepared. The specific components and mixture ratios of the coating solution used in the present embodiment can be freely selected within the range to achieve the object of the present invention. In preferred practice, the solution contains: a water-insoluble polymer having a carboxyl group at a level of 0.1 to 10 parts by weight, preferably 0.5 to 5 parts by weight, and more preferably 1 to 2 parts by weight; a polyfunctional active compound at a level of 0.01 to 5 parts by weight, preferably 0.05 to 3 parts by weight, and more preferably 0.1 to 1 part by weight; a surfactant at a level of 0.01 to 5 parts by weight, preferably 0.05 to 1 part by weight; and an organic solvent at a level of 1 to 100 parts by weight, preferably 2 to 99 parts by weight, and more preferably 20 to 31 parts by weight.

Then, at the coating solution preparation step, hydroxypropylmethylcellulose phthalate, polyisocyanate and surfactant were mixed by known means and dissolved in acetone to obtain a coating solution.

According to the present embodiment, the coating step is performed in the following manner. First, a desired amount of the coating solution is dropped from the opening 29 into the nozzle portion 34.

Then, using a spin coater (not shown), the tool body 12 is rotated in the horizontal direction about a point located axially rearward from the nozzle unit 34, so that centrifugal force acts from the side of the platform 20 toward the front end opening 40 of the nozzle unit 34. Due to this centrifugal force, the coating solution is transported from the base end opening 38 toward the leading end opening 40 and is spread by surface tension to cover the entire face of the through-hole 36, while the excess coating solution is discharged through the leading end opening 40. As a result, the coating solution is applied to the entire surface of the through-hole 36 of the nozzle unit 34 to have a substantially uniform thickness.

The coating is then subjected to a crosslinking step. In this example, the crosslinking reaction by the polyisocyanate in the coating solution was accelerated by heat treatment at 80 ℃ for 1 hour.

Next, as a chemical reaction step for hydrophilizing the coating, the entire nozzle portion 34 was immersed in a 1% aqueous sodium bicarbonate solution for 10 minutes to neutralize the coating. Thereby, the carboxyl group of the hydroxypropylmethylcellulose phthalate in the coating layer is neutralized, providing hydrophilicity to the coating layer.

Once neutralization is complete, the tool body 12, including the snout 34, is subjected to a cleaning process and a drying process to complete the formation of the coating on the insertion tool 10.

The coating forming means described herein are merely exemplary, and any mode described hereinbefore as an embodiment of the invention relating to the manufacturing method of the medical tool is suitable as a solution for the purpose of forming a coating on the insertion tool 10. In the present embodiment, the coating layer is formed only on the surface of the through-hole 36 of the nozzle unit 34; alternatively, however, the coating can be formed on the entire surface of the insertion tool 10, or only some other portion thereof.

Once the coating of the through hole 36 is completed, the plunger 14 provided as the pushing member is inserted into the tool body 12 from the rear and slid through the through hole 15. A tube 44, which is substantially annular in plan view, is attached to the front end portion of the plunger 14. The tube 44 is designed to be easily deformed at a lengthwise middle portion thereof positioned at the front end of the plunger 14.

In the insertion tool 10 having the above structure, first, with the front end portion of the plunger 14 in the initial position (the aforementioned position shown in fig. 1) that has been inserted from the rear of the tool main body 12, the intraocular lens 26 is placed on the seating surface 30. The opening 29 of the stage 20 is then covered by the cap portion 32 so that the intraocular lens 26 is positioned to be accommodated within the tool body 12.

The insertion tool 10 according to this embodiment is then subjected to sterilization treatment or the like with the intraocular lens 26 accommodated therein, and then packaged and shipped.

To insert the intraocular lens 26 into an eye using the insertion tool 10 according to the present embodiment, first, the plunger 14 is pushed inward with the leading end portion of the nozzle portion 34 inserted through a surgical incision formed in eye tissue. The tube 44 of the plunger 14 thus contacts the holding portion 28 of the intraocular lens 26 resting on the resting surface 30 and guides the intraocular lens 26 toward the base end opening 38.

In preferred practice, a suitable lubricant is injected into the interior of the platform 20 or nozzle unit 34 prior to ejecting the intraocular lens 26. In the present embodiment, in particular, an injection hole 46 formed through the cover portion 32 in the thickness direction is formed to allow injection to occur through the injection hole 46 with the cover portion 32 closed. In a preferred practice, sodium hyaluronate is used as a lubricant.

The intraocular lens 26 that has been guided into the nozzle unit 34 from the base end opening 38 is positioned in such a manner that the protruding guide portion 42 abuts the widthwise central portion of the main body 27, causing bowing deformation so that the main body 27 becomes upwardly convex. The intraocular lens 26 inside the through hole 36 is thereby given an initial deformation conforming to the shape of the through hole 36, and is pushed toward the leading end opening 40.

Further pushing the plunger 14 inward causes the intraocular lens 26 to deform into a tapered shape, and then is pushed out of the insertion tool 10 through the front end opening 40 and inserted into the eye.

According to the insertion tool 10 of the present embodiment, enhanced lubricity is imparted to the inside of the through hole 36 due to the coating layer formed on the surface of the through hole 36 in the nozzle unit 34, thereby preventing improper deformation and sticking between the surface of the nozzle unit 34 and the intraocular lens 26. This eliminates the problem that the intraocular lens 26 becomes immovably stuck inside the through-hole 36 during pushing the plunger 14 or the intraocular lens 26 loses its deformed state, so that the consistent insertion of the intraocular lens 26 occurs smoothly.

In the present embodiment, the formation of the hydrophilic coating on the surface of the medical tool 10 is accomplished by a simple measure of forming a coating of a water-insoluble polymer having a carboxyl group and subjecting the coating to a neutralization treatment to provide hydrophilicity thereto. In particular, it is not necessary to perform a dual coating having a polymer-based layer and a hydrophilic polymer layer to produce a hydrophilic coating, because high lubricity and excellent hydrophilic coating ability are provided by a single coating structure consisting of only a single layer. Therefore, the intraocular lens insertion tool 10 having excellent lubricity can be obtained without increasing the number of manufacturing steps in any way.

By crosslinking the coating solution by means of polyfunctional reactive compounds, in particular polyisocyanates, elution of the coating components into the solution is prevented even in the case of contact of the coating with solutions such as lubricants. So that the coating properties can be advantageously maintained during use.

Although preferred embodiments of the invention relating to the method of manufacturing the medical tool and the invention relating to the intraocular lens insertion tool have been described in detail, these are merely exemplary, and the present invention should not be construed as being limited in any way by the specific disclosure in these embodiments.

For example, according to the foregoing embodiment, the chemical reaction treatment of the coating layer includes neutralization treatment using an aqueous sodium bicarbonate solution or the like; however, as an alternative to the neutralization treatment, a layer of sodium hyaluronate may be applied to the surface of the coating to provide further hydrophilicity. Alternatively, sodium hyaluronate may be added to the neutralization solution in the foregoing neutralization treatment to provide better lubricity.

Various modifications, alterations and improvements of the present invention which are not separately set forth herein will occur to those skilled in the art and are intended to be within the scope of the present invention without departing from the spirit of the invention.

Examples of the invention

The following description of several examples of the invention provides a more particular understanding of the invention, but the invention is in no way limited to the disclosure in these examples. It should be understood that various modifications, alterations and adaptations of the present invention beyond those taught by the following examples and detailed description herein may occur to one skilled in the art without departing from the spirit of the present invention.

First, an intraocular lens insertion tool 10 made of polypropylene as shown in fig. 1 is prepared. Coating materials of the compositions indicated in table 1 below were also prepared.

[ Table 1]

Specifically, in examples 1 to 6, 1 to 1.25 parts by weight of hydroxypropylmethylcellulose phthalate or 1.5 to 2 parts by weight of cellulose acetate phthalate was contained as a water-insoluble polymer having a carboxyl group. In each example, 0.2 to 1 part by weight of polyisocyanate is contained as the polyfunctional reactive compound. More specifically, AQUANATE 100, which is a water dispersible polyisocyanate manufactured by Nippon polyurethane industries, Ltd., or CORONATAEHXR, which is a hexamethylene diisocyanate polymer manufactured by Nippon polyurethane industries, Ltd., was used. The organic solvent is acetone contained in an amount of 20 to 31 parts by weight. In examples 3, 4 and 6, the surfactant is TL-10, which is sorbitan polyoxyethylene (20) ether monolaurate manufactured by heliochemical corporation, or glyceryl monostearate, respectively contained in an amount of 0.05 to 1 part by weight.

After combining the coating materials having the above compositions to prepare a coating solution, a 100 μ L sample volume (aliquot) was dispensed to the nozzle unit 34 of the insertion tool 10 using a pipette system. The dispensed sample volume was then spun rapidly at 1500rpm for 5 seconds using a spin coater to spread the solution across the surface of the nozzle block 34 and remove excess coating solution through the front end opening 40. Subsequently, after causing crosslinking by heat treatment at 80 ℃ for 1 hour, the nozzle unit 34 was immersed in a 1% aqueous sodium bicarbonate solution for 10 minutes to effect neutralization treatment. The insertion tool 10 is then cleaned and dried.

The coated intraocular lens insertion tool 10 prepared in the above manner is then tested for insertion of an intraocular lens 26. Specifically, first, a sodium hyaluronate preparation manufactured by showa pharmaceutical chemical corporation is applied to the nozzle portion 34 in an appropriate amount as a viscoelastic material for ophthalmic surgery; and the acrylate folded intraocular lens 26 is set thereon and then pushed out using the plunger 14.

In the tests, as comparative examples 1 and 2, samples were prepared using coating materials containing materials of the same composition as in example 1 except for examples 1 to 6 without being subjected to chemical reaction treatment; and the sample is prepared by subjecting the insertion tool 10 to only the alkali treatment without providing any coating. The samples were evaluated for lubricity during insertion in the same manner as in examples 1 to 6.

Evaluation results of lubricity during push-out of intraocular lens 26 in examples 1 to 6 and comparative examples 1 and 2 using symbols in table 1And Δ, and × are shown. In Table 1, the samples provided good lubricity and smooth pushout are shownRepresents; samples with no problem with lubricity but with little detectable resistance during ejection are indicated by ∘; a sample having satisfactory lubricity but exhibiting some sticking with the intraocular lens 26 staying inside the nozzle portion 34 is denoted by Δ; a sample lacking any lubricity to hinder the intraocular lens 26 from being pushed out of the nozzle unit 34 is represented by x.

As is apparent from the results of table 1, it is clear that good lubricity is obtained in all of examples 1 to 6, while no lubricity is obtained in comparative example 1 or 2.

Specifically, it was shown that by the combination of the specific coating material components of examples 1 to 6 and the alkali treatment performed as a chemical reaction treatment, exceptionally good hydrophilicity and lubricity were obtained.

Claims (7)

1. A manufacturing method of a medical tool adapted to impart hydrophilicity and lubricity to a surface of the medical tool by forming a coating layer on the surface, the manufacturing method comprising:

a coating solution preparing step of dissolving at least a water-insoluble polymer having a carboxyl group selected from the group consisting of hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, cellulose acetate phthalate and a mixture thereof and a polyfunctional active compound in an organic solvent to obtain a coating solution;

a coating step in which the coating solution is applied to the surface of the medical tool to form the coating layer;

a crosslinking step in which the coating undergoes crosslinking; and

a chemical reaction step in which a chemical reaction treatment is performed to cause hydrophilization of the coating layer that has been crosslinked, the chemical reaction treatment being an alkali treatment.

2. The method for manufacturing a medical tool according to claim 1, wherein the coating solution comprises 0.1 to 10 parts by weight of the water-insoluble polymer having a carboxyl group, 0.01 to 5 parts by weight of the polyfunctional active compound, and 1 to 100 parts by weight of the organic solvent.

3. The method of manufacturing a medical tool according to claim 1, wherein the polyfunctional reactive compound is selected from the group consisting of isocyanates, epoxides, acid chlorides, anhydrides, triazines, reactive esters, and mixtures thereof.

4. The method for manufacturing a medical tool according to claim 1, wherein the coating solution contains a surfactant.

5. The method of manufacturing a medical tool according to claim 1, wherein the coating step further comprises the steps of: after the coating solution is applied to the surface of the medical implement, the coating solution is aspirated or the medical implement is rotated to subject the coating solution to centrifugal force in order to spread the coating solution in a layer on the surface of the medical implement and to remove excess coating solution from the surface of the medical implement.

6. The method of manufacturing a medical tool according to claim 1, wherein the medical tool comprises an intraocular lens insertion tool.

7. An intraocular lens insertion tool comprising a generally tubular tool main body accommodating an intraocular lens therein, and adapted to move the intraocular lens axially forward by an ejection member inserted into the tool main body from the axial rearward direction while causing the lens to deform to a smaller size and eject the lens into the eye through an insertion tube portion provided at an axial front end portion of the tool main body, the intraocular lens insertion tool being characterized in that:

the surface of the inside of the insertion tube portion is imparted with hydrophilicity and lubricity by a coating layer formed thereon; and is

The coating consists of a cross-linked chemically treated film formed by the steps of: a coating solution preparing step of dissolving at least a water-insoluble polymer having a carboxyl group selected from the group consisting of hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, cellulose acetate phthalate and a mixture thereof and a polyfunctional active compound in an organic solvent to obtain a coating solution; a coating step in which a coating solution is applied to the surface of the medical tool to form the coating layer; a crosslinking step in which the coating undergoes crosslinking; and a chemical reaction step in which a chemical reaction treatment is performed to cause hydrophilization of the crosslinked coating layer, the chemical reaction treatment being an alkali treatment.